Skip to main content
  • ASM
    • Antimicrobial Agents and Chemotherapy
    • Applied and Environmental Microbiology
    • Clinical Microbiology Reviews
    • Clinical and Vaccine Immunology
    • EcoSal Plus
    • Eukaryotic Cell
    • Infection and Immunity
    • Journal of Bacteriology
    • Journal of Clinical Microbiology
    • Journal of Microbiology & Biology Education
    • Journal of Virology
    • mBio
    • Microbiology and Molecular Biology Reviews
    • Microbiology Resource Announcements
    • Microbiology Spectrum
    • Molecular and Cellular Biology
    • mSphere
    • mSystems
  • Log in
  • My alerts
  • My Cart

Main menu

  • Home
  • Articles
    • Current Issue
    • Accepted Manuscripts
    • Archive
    • Minireviews
  • For Authors
    • Submit a Manuscript
    • Scope
    • Editorial Policy
    • Submission, Review, & Publication Processes
    • Organization and Format
    • Errata, Author Corrections, Retractions
    • Illustrations and Tables
    • Nomenclature
    • Abbreviations and Conventions
    • Publication Fees
    • Ethics Resources and Policies
  • About the Journal
    • About IAI
    • Editor in Chief
    • Editorial Board
    • For Reviewers
    • For the Media
    • For Librarians
    • For Advertisers
    • Alerts
    • RSS
    • FAQ
  • Subscribe
    • Members
    • Institutions
  • ASM
    • Antimicrobial Agents and Chemotherapy
    • Applied and Environmental Microbiology
    • Clinical Microbiology Reviews
    • Clinical and Vaccine Immunology
    • EcoSal Plus
    • Eukaryotic Cell
    • Infection and Immunity
    • Journal of Bacteriology
    • Journal of Clinical Microbiology
    • Journal of Microbiology & Biology Education
    • Journal of Virology
    • mBio
    • Microbiology and Molecular Biology Reviews
    • Microbiology Resource Announcements
    • Microbiology Spectrum
    • Molecular and Cellular Biology
    • mSphere
    • mSystems

User menu

  • Log in
  • My alerts
  • My Cart

Search

  • Advanced search
Infection and Immunity
publisher-logosite-logo

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Accepted Manuscripts
    • Archive
    • Minireviews
  • For Authors
    • Submit a Manuscript
    • Scope
    • Editorial Policy
    • Submission, Review, & Publication Processes
    • Organization and Format
    • Errata, Author Corrections, Retractions
    • Illustrations and Tables
    • Nomenclature
    • Abbreviations and Conventions
    • Publication Fees
    • Ethics Resources and Policies
  • About the Journal
    • About IAI
    • Editor in Chief
    • Editorial Board
    • For Reviewers
    • For the Media
    • For Librarians
    • For Advertisers
    • Alerts
    • RSS
    • FAQ
  • Subscribe
    • Members
    • Institutions
Microbial Immunity and Vaccines

Host Defense against Mycobacterium aviumDoes Not Have an Absolute Requirement for Major Histocompatibility Complex Class I-Restricted T Cells

Luiz E. Bermudez, Mary Petrofsky
Luiz E. Bermudez
Kuzell Institute for Arthritis and Infectious Diseases, California Pacific Medical Center Research Institute, San Francisco, California 94115
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mary Petrofsky
Kuzell Institute for Arthritis and Infectious Diseases, California Pacific Medical Center Research Institute, San Francisco, California 94115
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI: 10.1128/IAI.67.6.3108-3111.1999
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

ABSTRACT

The role of CD8+ T cells was evaluated in a mouse model of disseminated Mycobacterium avium infection. C57BL/6J and C57BL/6Jβ2−/−(β2−/−) mice were infected intravenously, and the number of viable bacteria in each liver and spleen was determined. No significant difference between the number of bacteria in the two strains of mice was observed at 2, 4, 6, and 8 weeks after infection. Histopathological examination of granulomas from C57BL/6J and β2−/− mice did not show any difference either in the number of organisms per granuloma or in the size of the granulomas. Investigation of the cytokine profile in the spleen demonstrated that the β2−/− strain of mice produced a significantly lower amount of gamma interferon at 8 weeks after infection and significantly increased concentrations of tumor necrosis factor alpha compared with that from the wild-type mouse. Interleukin-12 and transforming growth factor β1 levels did not differ between the two strains of mice at 2, 4, 6, and 8 weeks. Although previous work had found that host response againstMycobacterium tuberculosis involves major histocompatibility complex class I-restricted T cells, our results indicate that chronic deficiency of CD8+ T cells does not lead to a different expression of the disease and that if CD8+ T cells are involved in the host response, their function can be assumed by other immune cells.

Organisms of the Mycobacterium avium complex are intracellular pathogens associated with disseminated disease in patients in advanced stages of AIDS (15, 17). Immunity to M. avium initially requires the stimulation of NK cells (5, 7) and later the activation of specific T lymphocytes, which respond to the infection by secreting cytokines that increase the ability of monocytes and macrophages to inhibit M. avium growth. In addition, a number of researchers point to a plausible role of CD8+cytotoxic cells against infected monocytes or macrophages in the lysing of infected cells (1, 20).

There is substantial experimental evidence that CD4+T cells are important for an effective host defense againstM. avium (1, 20). The role of CD8+ T lymphocytes, however, is controversial. Cytotoxic CD8+ T cells have been shown to play an important role in the host defense against Mycobacterium tuberculosis as demonstrated both by studies of CD8 T-lymphocyte depletion by specific antibodies and by studies with β2 microglobulin knockout (KO) (also referred to in this work as β2−/−) mice (13, 16). In contrast, no information is available about the role of CD8+ T cells on M. avium growth in mouse models of infection. More recently, Saunders and Cheers (23) showed that in a mouse intranasal model ofM. avium infection, depletion of CD8+ T lymphocytes from infected mice had no effect on bacterial growth and CD4+ T-cell activation, indicating that the immune response against M. avium may differ from the response againstM. tuberculosis.

In this study, we evaluated the role of CD8+ T cells in the host defense against M. avium by using the β2−/− mice, devoid of major histocompatibility complex (MHC) class I-restricted T cells, including cytotoxic T lymphocytes, and CD1+ restricted cytotoxic T cells (no murine equivalent to human CD1+ has previously been described).

MATERIALS AND METHODS

M. avium. M. avium 101 (serovar 1) was isolated from the blood of a patient with AIDS. Strain 101 is a virulent strain in mice and is associated with reproducible levels of tissue infection in C57BL/6J mice. Mycobacteria were cultured on Middlebrook 7H11 agar (Difco Laboratories, Detroit, Mich.) for 10 days at 37°C. Transparent colonies were harvested and resuspended in Hanks’ balanced salt solution and washed twice. The final suspension was then adjusted to 108 bacteria/ml according to a McFarland turbidimetric standard. A sample obtained from the final suspension was plated to confirm the number of bacteria in the inoculum.

Mice.Female, 6- to 8-week-old, C57BL/6J and C57BL/6J β2−/− (β2−/−) mice were purchased from Jackson Laboratory (Bar Harbor, Maine). Mice were infected with 5 × 107 viable bacteria injected into the tail vein. We decided to use this inoculum based on previous experience with a variety of inocula and preliminary experiments using 105, 107, and 108 bacteria as inocula (data not shown). All mice were maintained in a pathogen-free environment and were found to be free of the four more common mouse pathogens (data not shown). Experiments were repeated twice, and 16 or 17 mice were used per group for each time point.

Harvesting.Spleens and livers were removed aseptically at 2, 4, 6, and 8 weeks and, after weighing, were homogenized in 5 ml of Middlebrook 7H9 broth as previously described (8). Serial 10-fold dilutions were plated onto 7H11 agar supplemented with oleic acid, albumin, dextrose, and catalase. Colonies on the plates were counted after 10 to 14 days of incubation at 37°C and 5% CO2.

Cytokine assays.Spleens were obtained from infected and uninfected mice at 2, 4, 6, and 8 weeks and were prepared as previously described (2). Because splenic macrophages are heavily infected, we measured the extracellular release of cytokines by splenocytes (lymphocytes plus macrophages). Cytokines in the supernatant were obtained after 24 h and filtered through a 0.45-μm-pore-size filter, and gamma interferon (IFN-γ), interleukin-10 (IL-10), IL-12, tumor necrosis factor alpha (TNF-α) (Biosource, Camarillo, Calif.), and transforming growth factor β1 (TGF-β1) were measured by enzyme-linked immunosorbent assay (R and D Systems, Minneapolis, Minn.) as recommended by the manufacturers.

Histopathology.Sections (5 μm thick) from paraffin blocks containing livers and spleens were cut and stained with hematoxylin and eosin or by the Ziehl-Neelsen method for acid-fast bacilli (AFB). The mean number of AFB was evaluated by counting the organisms with granulomas in 20 random fields per section (magnification, ×400).

Statistical analysis.The results were represented as means ± standard errors. The comparison between experimental groups and control was done by using analysis of variance at the same time point. A P value of <0.05 was considered significant.

RESULTS

M. avium infection in β2−/−and control mice.A total of 16 or 17 C57BL/6J and 16 or 17 β2−/− mice were infected with 5 × 106M. avium organisms intravenously per experimental group for each time point. Mice were monitored for 2 to 8 weeks. No mortality was observed in either group at 2 weeks; however, 1 of 17 β2−/− mice died and 3 of 17 control C57BL/6J mice died after 4 weeks (P > 0.05 for all comparisons). At 6 weeks, 4 of 16 C57BL/6J mice died and 1 of 16 of β2−/− mice died, while 4 of 16 died at 8 weeks in the control group and 4 of 16 β2−/− mice died.

As shown in Table 1, the numbers of viable bacteria in both liver and spleen at 2, 4, 6, and 8 weeks were similar between C57BL/6J and C57BL/6J β2−/−mice. Limited data obtained with 105, 107, and 108 bacteria showed similar results to the ones obtained with 106 organisms (data not shown).

View this table:
  • View inline
  • View popup
Table 1.

Number of viable bacteria in mouse organs following infection

Histopathology studies.Histopathologic sections of spleen and liver from both C57BL/6J control and β2−/−mice had well-demonstrated granulomas composed of epithelioid macrophages. The numbers of AFB in granulomas from C57BL/6J and β2−/− mice were similar at both 2, 4, and 6 weeks (data not shown) and 8 weeks (Fig.1 and Table2). By 8 weeks the number of bacteria in spleen was significantly greater than that by 2 and 4 weeks, and some of the granulomas were confluent.

Fig. 1.
  • Open in new tab
  • Download powerpoint
Fig. 1.

Histopathology (hematoxylin and eosin stain) of spleens C57BL/6J (A) and β2−/− (B) mice at 8 weeks after infection. Ziehl-Neelsen staining of necrotizing granulomas at 8 weeks after infection in C57BL/6J (C) and β2−/− (D) mice. Magnification, ×170.

View this table:
  • View inline
  • View popup
Table 2.

Number of bacteria per granuloma in mouse spleen after infection

Cytokine production.IFN-γ, IL-12, and TNF-α have been shown to be important in the control of M. avium infection (6, 12, 24), whereas IL-10 and TGF-β1 have been associated with the progression of disease both in vitro and in vivo (3, 4).

As shown in Table 3, the cytokine profile did not differ significantly between splenic cells from C57BL/6J control and β2−/− mice at 2 and 4 weeks after infection; however, significant differences in the levels of IFN-γ and TNF-α were observed at week 8 of infection.

View this table:
  • View inline
  • View popup
Table 3.

Cytokine profiles in mice

DISCUSSION

The susceptibility of AIDS patients with low CD4+T-cell counts to M. avium infection illustrates the importance of this T-cell subpopulation in the mechanisms of acquired resistance against M. avium infection. Our present results with β2 microglobulin KO mice confirm the finding of previous studies using specific antibodies to deplete CD8+T-cell population that CD8+ T lymphocytes are not an absolute requirement for the control of M. avium infection (1, 23).

In contrast to their role in M. avium infection, CD8+ T cells appear to play a role in immunity of M. tuberculosis-infected mice (13, 16). These observations suggest that the immune mechanisms involved in the host defense against these pathogens are different. For example, there is plenty of evidence that NK cells play an important role in the innate immune response against M. avium (5, 6) but have no established role in M. tuberculosis infection (11). Recent work has shown that lack of both perforin and granzyme, which represent known mechanisms of CD8+ T-cell-mediated cytotoxicity, does not influence the outcome of M. tuberculosis infection in mice (10, 18), raising the possibility that cytokine production is more likely the way CD8+ cells participate in the defense against M. tuberculosis. More recently it was also demonstrated that production of IFN-γ is a major function of CD8+ T cells in tuberculosis (26). Results with the M. aviummodel, however, demonstrate that CD8+ T-cell-mediated cytotoxicity is not an obligatory mechanism of host defense against the organism. In addition, production of cytokines by CD8+ T cells does not appear to participate in the immune response. It is interesting that β2−/− mice produce significantly less IFN-γ than the wild-type mice at 8 weeks, without any impact in the level of infection. The drop in IFN-γ concentration does not seem to be dependent upon the IL-12 level. Perhaps the increased TNF-α levels at 8 weeks are compensatory for the drop in IFN-γ levels. It is intriguing that the role of CD8+ T cells in the host defense is completely different in infections withM. avium and M. tuberculosis, although it has also been demonstrated that lack of MHC class I expression did not compromise the ability to control Mycobacterium bovis BCG infection (13). While M. aviuminfections of SCID mice are slow to progress and do not end in augmented mortality (1), infection of SCID mice withM. tuberculosis is fatal within approximately 30 days (11). It is possible that the well-known hypertrophic NK cell compartment in SCID mice protects against M. avium. In our experiments, greater mortality was seen in control mice (wild type) than in CD8 KO mice. It is possible that CD8 T cells, although they do not participate in the defense against M. aviuminfection, do secrete or stimulate the secretion of inflammatory cytokines which ultimately participate in mortality.

The finding that splenic cells from β2−/−mice and C57BL/6J mice produced equal amounts of IFN-γ, TNF-α, IL-12, IL-10, and TGF-β1 at 2 and 4 weeks after infection with M. avium was unexpected. By 8 weeks, however, a significant difference between IFN-γ produced by control mice and KO mice was observed. Work by our and other laboratories has suggested the importance of IFN-γ and TNF-α as key players in the host defense against M. avium (12, 24). Saunders and Cheers, using an intranasal infection model for M. avium lung infection, have determined that CD8+ T cells from mice infected with M. avium do not produce IFN-γ (23). This observation was in contrast to the reports showing that both CD4+ and CD8+ T cells produce IFN-γ following activation by M. tuberculosis infection (26).

The results of our study were supported by the histopathologic sectioning of the spleens, which demonstrated that granulomas from β2−/− mice and C57BL/6J mice did not differ in size or number of organisms contained. The lack of evidence for CD8+ T-cell contribution in the host defense againstM. avium is consistent with the intravacuolar residence of M. avium in macrophages (25) and is similar to the role of CD8+ T cells in the protection against Salmonella enterica infection (14). Although experimental evidence clearly demonstrates that CD8+ T cells respond to Salmonella antigens in vivo, the relevance of antigen-specific CD8+ T cells has not been proved. In contrast, CD8+ T cells have been shown to be important for the defense against Listeria monocytogenes (21), an intracellular pathogen that lyses its vacuole membrane and lives within the cytoplasm.

A report by McDonough and Kress (19) showed thatM. tuberculosis can escape from vacuoles in macrophages. Although this observation has not been confirmed by other laboratories (9, 22), it may be that under certain circumstances (for example, bacterial growth conditions before the uptake by macrophages) it may occur, which would better explain the differences observed between CD8+ T-cell roles in M. avium and M. tuberculosis infections. Although a recent study (27) suggests that β2−/−mice possess a limited repertoire of self-MHC class I-restricted CD8+ T cells, which can be explained by selection on the remaining low levels of MHC class I, the different results obtained with M. avium and M. tuberculosis indicate that at least CD8+ T-cell participation in host defense againstM. avium is not indispensable. Clear evidence exists, for example, for the importance of CD8+ T cells in L. monocytogenes infection, as well as in M. tuberculosisinfection. For Salmonella and M. avium, CD8+ T cells appear not to participate in the immunity against the pathogens, although antigen-specific CD8+T-cell clones can be identified.

In summary, we have demonstrated in β2−/−mice that CD8+ T cells are not essential for the host defense against M. avium. Further studies will be necessary to confirm these findings in an oral infection model more similar to the infection in humans.

ACKNOWLEDGMENTS

We thank Karen Allen for preparing the manuscript.

This work was supported by contract NOI-AI-25140 of the National Institutes of Health.

Notes

Editor: R. N. Moore

FOOTNOTES

    • Received 16 November 1998.
    • Returned for modification 4 January 1999.
    • Accepted 29 March 1999.
  • Copyright © 1999 American Society for Microbiology

REFERENCES

  1. 1.↵
    1. Appelberg R.,
    2. Castro A. G.,
    3. Pedrosa J.,
    4. Silva R. A.,
    5. Orme I. M.,
    6. Minoprio P.
    Role of gamma interferon and tumor necrosis factor alpha during T-cell-independent and dependent phases of Mycobacterium avium infection.Infect. Immun.62199439623971
    OpenUrlAbstract/FREE Full Text
  2. 2.↵
    1. Azouaou N.,
    2. Petrofsky M.,
    3. Young L. S.,
    4. Bermudez L. E.
    Mycobacterium avium infection in mice is associated with time-related expression of TH1 and TH2 CD4+ T-lymphocyte response.Immunology911997414420
    OpenUrlCrossRefPubMedWeb of Science
  3. 3.↵
    1. Bermudez L. E.
    Production of transforming growth factor-beta by Mycobacterium avium-infected human macrophages is associated with unresponsiveness to IFN-gamma.J. Immunol.150199318381845
    OpenUrlAbstract
  4. 4.↵
    1. Bermudez L. E.,
    2. Champsi J.
    Infection with Mycobacterium avium induces production of interleukin-10 (IL-10), and administration of anti-IL-10 antibody is associated with enhanced resistance to infection in mice.Infect. Immun.61199330933096
    OpenUrlAbstract/FREE Full Text
  5. 5.↵
    1. Bermudez L. E.,
    2. Kolonoski P.,
    3. Young L. S.
    Natural killer cell activity and macrophage dependent inhibition of growth or killing of Mycobacterium avium complex in a mouse model.J. Leukoc. Biol.471990135142
    OpenUrlPubMedWeb of Science
  6. 6.↵
    1. Bermudez L. E.,
    2. Wu M.,
    3. Young L. S.
    Interleukin-12-stimulated natural killer cells can activate human macrophages to inhibit growth of Mycobacterium avium complex.Infect. Immun.63199540994105
    OpenUrlAbstract/FREE Full Text
  7. 7.↵
    1. Bermudez L. E.,
    2. Young L. S.
    Natural killer cell dependent mycobacteriostatic and mycobactericidal activity in human macrophages.J. Immunol.1461991265269
    OpenUrlAbstract
  8. 8.↵
    1. Champsi J.,
    2. Young L. S.,
    3. Bermudez L. E.
    Production of TNF-α, IL-6 and TGFβ and expression of receptors for TNFα and IL-6 during murine Mycobacterium avium infection.Immunology841995549554
    OpenUrlPubMed
  9. 9.↵
    1. Clemens D. L.,
    2. Horwitz M. A.
    Characterization of the Mycobacterium tuberculosis phagosome and evidence that phagosomal maturation is inhibited.J. Exp. Med.1811995257270
    OpenUrlAbstract/FREE Full Text
  10. 10.↵
    1. Cooper A. M.,
    2. D’Souza C.,
    3. Frank A. A.,
    4. Orme I. M.
    The course of Mycobacterium tuberculosis infection in the lungs of mice lacking expression of perforin- or granzyme-mediated cytolytic mechanisms.Infect. Immun.65199713171320
    OpenUrlAbstract/FREE Full Text
  11. 11.↵
    1. Cooper A. M.,
    2. Roberts A. D.,
    3. Rhoades E. R.,
    4. Callahan J. E.,
    5. Getzy D. M.,
    6. Orme I. M.
    The role of interleukin-12 in acquired immunity to Mycobacterium tuberculosis infection.Immunology841995423432
    OpenUrlPubMedWeb of Science
  12. 12.↵
    1. Doherty T. M.,
    2. Sher A.
    Defects in cell-mediated immunity after chronic, but not innate, resistance of mice to Mycobacterium avium infection.J. Immunol.158199748224831
    OpenUrlAbstract
  13. 13.↵
    1. Flynn J. L.,
    2. Goldstein M. M.,
    3. Triebold K. J.,
    4. Koller B.,
    5. Bloom B. R.
    Major histocompatibility complex class I-restricted T cells are required for resistance to Mycobacterium tuberculosis infection.Proc. Natl. Acad. Sci. USA8919921201312017
    OpenUrlAbstract/FREE Full Text
  14. 14.↵
    1. Hess J.,
    2. Kaufmann S. H. E.
    Salmonella enterica infection.Res. Immunol.361997581586
    OpenUrl
  15. 15.↵
    1. Horsburgh C. R. Jr.
    Mycobacterium avium complex in the acquired immunodeficiency syndrome (AIDS).N. Engl. J. Med.324199113321338
    OpenUrlCrossRefPubMedWeb of Science
  16. 16.↵
    1. Howard A. D.,
    2. Trans O. J.,
    3. Weisbrode S. E.,
    4. Zwilling B. S.
    Plenotypic changes in T cell populations during the reactivation of tuberculosis in mice.Clin. Exp. Immunol.1111998309315
    OpenUrlCrossRefPubMed
  17. 17.↵
    1. Inderlied C. B.,
    2. Kemper C. A.,
    3. Bermudez L. E.
    The Mycobacterium avium complex.Clin. Microbiol. Rev.61993266310
    OpenUrlAbstract/FREE Full Text
  18. 18.↵
    1. Laochumroonvapong P.,
    2. Wang J.,
    3. Liu C. C.,
    4. Ye W.,
    5. Moreira A. L.,
    6. Elkon K. B.,
    7. Freedman V. H.,
    8. Kaplan G.
    Perforin, a cytotoxic molecule which mediates cell necrosis, is not required for the early control of mycobacterial infection in mice.Infect. Immun.651997127132
    OpenUrlAbstract/FREE Full Text
  19. 19.↵
    1. McDonough K.,
    2. Kress Y.
    Cytotoxicity for lung epithelial cells is a virulence-associated phenotype of Mycobacterium tuberculosis.Infect. Immun.63199548024811
    OpenUrlAbstract/FREE Full Text
  20. 20.↵
    1. Orme I. M.,
    2. Furney S. K.,
    3. Roberts A. D.
    Dissemination of enteric Mycobacterium avium infections in mice rendered immunodeficient by thymectomy and CD4 depletion or by prior infection with murine AIDS retrovirus.Infect. Immun.60199247474753
    OpenUrlAbstract/FREE Full Text
  21. 21.↵
    1. Roberts A. D.,
    2. Ordway D. J.,
    3. Orme I. M.
    Listeria monocytogenes infection in β2 microglobulin-deficient mice.Infect. Immun.61199311131116
    OpenUrlAbstract/FREE Full Text
  22. 22.↵
    1. Russell D. G.
    Mycobacterium and Leishmania: stowaways in the endosomal network.Trends Cell Biol.51995125128
    OpenUrlCrossRefPubMedWeb of Science
  23. 23.↵
    1. Saunders B. M.,
    2. Cheers C.
    Inflammatory response following intranasal infection of Mycobacterium avium complex: role of T-cell subsets and interferon gamma.Infect. Immun.63199522822287
    OpenUrlAbstract/FREE Full Text
  24. 24.↵
    1. Saunders B. M.,
    2. Zhan Y.,
    3. Cheers C.
    Interleukin-12 is involved in resistance of mice to Mycobacterium avium complex infection.Infect. Immun.63199540114015
    OpenUrlAbstract/FREE Full Text
  25. 25.↵
    1. Sturgill-Koszycki S.,
    2. Schlesinger P. H.,
    3. Chakraborty P.,
    4. Haddix P. L.,
    5. Collins H. L.,
    6. Fok A. K.,
    7. Allen R. D.,
    8. Gluck S. L.,
    9. Heuser J.,
    10. Russell D. G.
    Lack of acidification in Mycobacterium phagosomes produced by exclusion of the vesicular proton-ATPase.Science2631994678681
    OpenUrlAbstract/FREE Full Text
  26. 26.↵
    1. Tascon R. E.,
    2. Stavropoulos E.,
    3. Lukacs K. V.,
    4. Colston M. J.
    Protection against Mycobacterium tuberculosis infection by CD8+ T cells requires the production of gamma interferon.Infect. Immun.661998830834
    OpenUrlAbstract/FREE Full Text
  27. 27.↵
    1. Vugmeyster Y.,
    2. Glas R.,
    3. Perarnau B.,
    4. Lemonnier F. A.,
    5. Eisen H.,
    6. Ploegh H.
    Major histocompatibility complex (MHC) class I KdDb−/− deficient mice possess functional CD8+ T cells and natural killer cells.Proc. Natl. Acad. Sci. USA9519981249212497
    OpenUrlAbstract/FREE Full Text
View Abstract
PreviousNext
Back to top
Download PDF
Citation Tools
Host Defense against Mycobacterium aviumDoes Not Have an Absolute Requirement for Major Histocompatibility Complex Class I-Restricted T Cells
Luiz E. Bermudez, Mary Petrofsky
Infection and Immunity Jun 1999, 67 (6) 3108-3111; DOI: 10.1128/IAI.67.6.3108-3111.1999

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Print

Alerts
Sign In to Email Alerts with your Email Address
Email

Thank you for sharing this Infection and Immunity article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Host Defense against Mycobacterium aviumDoes Not Have an Absolute Requirement for Major Histocompatibility Complex Class I-Restricted T Cells
(Your Name) has forwarded a page to you from Infection and Immunity
(Your Name) thought you would be interested in this article in Infection and Immunity.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Host Defense against Mycobacterium aviumDoes Not Have an Absolute Requirement for Major Histocompatibility Complex Class I-Restricted T Cells
Luiz E. Bermudez, Mary Petrofsky
Infection and Immunity Jun 1999, 67 (6) 3108-3111; DOI: 10.1128/IAI.67.6.3108-3111.1999
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Top
  • Article
    • ABSTRACT
    • MATERIALS AND METHODS
    • RESULTS
    • DISCUSSION
    • ACKNOWLEDGMENTS
    • Notes
    • FOOTNOTES
    • REFERENCES
  • Figures & Data
  • Info & Metrics
  • PDF

KEYWORDS

CD8-Positive T-Lymphocytes
Histocompatibility Antigens Class I
Mycobacterium avium

Related Articles

Cited By...

About

  • About IAI
  • Editor in Chief
  • Editorial Board
  • Policies
  • For Reviewers
  • For the Media
  • For Librarians
  • For Advertisers
  • Alerts
  • RSS
  • FAQ
  • Permissions
  • Journal Announcements

Authors

  • ASM Author Center
  • Submit a Manuscript
  • Article Types
  • Ethics
  • Contact Us

Follow #IAIjournal

@ASMicrobiology

       

ASM Journals

ASM journals are the most prominent publications in the field, delivering up-to-date and authoritative coverage of both basic and clinical microbiology.

About ASM | Contact Us | Press Room

 

ASM is a member of

Scientific Society Publisher Alliance

 

American Society for Microbiology
1752 N St. NW
Washington, DC 20036
Phone: (202) 737-3600

Copyright © 2021 American Society for Microbiology | Privacy Policy | Website feedback

Print ISSN: 0019-9567; Online ISSN: 1098-5522