This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mohrs, M. Articles by Brombacher, F. Search for Related Content PubMed PubMed Citation Articles by Mohrs, M. Articles by Brombacher, F.

Infection and Immunity, April 2000, p. 1773-1780, Vol. 68, No. 4
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Interleukin-4 Receptor Alpha-Deficient BALB/c Mice Show an Unimpaired T Helper 2 Polarization in Response to Leishmania major Infection

Markus Mohrs,^1, Christoph Holscher,² and Frank Brombacher^1,2,*

Max Planck Institute for Immunobiology, Freiburg, Germany,¹ and Department of Immunology, Health Faculty, University of Cape Town, Cape Town, South Africa²

Received 7 September 1999/Returned for modification 2 November 1999/Accepted 30 December 1999

We recently generated interleukin-4 (IL-4) receptor alpha-deficient (IL-4R^/) BALB/c mice and showed evidence for a protective role of IL-13-mediated functions in leishmaniasis. In this study, we investigated the IL-4 expression and T helper 2 (Th2) development in Leishmania major-infected IL-4R^/ mice. Here we show that the early burst of IL-4 expression observed in L. major-infected BALB/c mice is independent of IL-4R-mediated functions. Subsequently, we confirmed an impaired Th2 development in vitro. Unexpectedly, during L. major infection, isolated CD4⁺ IL-4R^/ T cells expressed high IL-4- but low gamma interferon (IFN-)-specific mRNA, comparable to Th2-polarized BALB/c CD4⁺ cells and in contrast to Th1-polarized C57BL/6 CD4⁺ cells. Since antigen-specific restimulated popliteal lymph node cells (PLN) of IL-4R^/ mice also responded with high IL-4 but low IFN- production, comparable to Th2-polarized cells from wild-type BALB/c mice and in contrast to Th1-polarized C57BL/6 cells, these results suggested an unimpaired Th2 polarization during an established infection with L. major. To further define the observed IL-4 receptor-independent Th2 cell phenotype, we determined an independent Th2 marker, the IL-12 receptor beta-2 (IL-12R2)-specific transcript levels of CD4⁺ T cells. Confirming Th2 polarization in L. major-infected IL-4R^/ mice, comparable IL-12R2 message levels between CD4⁺ T cells from infected IL-4R^/ mice and Th2 cells from BALB/c mice were found, whereas Th1-polarized C57BL/6 cells showed strikingly increased IL-12R2 expression levels. These results indicate that signals mediated by the IL-4R are not necessary to induce and sustain an efficient IL-4 expression and Th2 polarization in L. major-infected BALB/c mice and suggest that IL-4R-independent mechanisms underlie the default Th2 development in L. major-infected BALB/c mice.

---

^* Corresponding author. Mailing address: University of Cape Town, Groote Schuur Hospital, Medical Faculty, Immunology Department, OMB, H47, Observatory, 7925, Cape Town, South Africa. Phone: (27)-21-4044013. Fax: (27)-21-4486116. E-mail: fbrombac{at}uctgsh1.uct.ac.za.

Present address: Howard Hughes Medical Institute and Department of Medicine and Microbiology/Immunology, University of California, San Francisco, San Francisco, Calif.

---

Infection and Immunity, April 2000, p. 1773-1780, Vol. 68, No. 4
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

This article has been cited by other articles:

• Nieuwenhuizen, N., Herbert, D. R., Lopata, A. L., Brombacher, F. (2007). CD4+ T Cell-Specific Deletion of IL-4 Receptor {alpha} Prevents Ovalbumin-Induced Anaphylaxis by an IFN-{gamma}-Dependent Mechanism. J. Immunol. 179: 2758-2765 [Abstract] [Full Text]  
• Nagase, H., Jones, K. M., Anderson, C. F., Noben-Trauth, N. (2007). Despite Increased CD4+Foxp3+ Cells within the Infection Site, BALB/c IL-4 Receptor-Deficient Mice Reveal CD4+Foxp3-Negative T Cells as a Source of IL-10 in Leishmania major Susceptibility. J. Immunol. 179: 2435-2444 [Abstract] [Full Text]  
• Misson, P., Brombacher, F., Delos, M., Lison, D., Huaux, F. (2007). Type 2 immune response associated with silicosis is not instrumental in the development of the disease. Am. J. Physiol. Lung Cell. Mol. Physiol. 292: L107-L113 [Abstract] [Full Text]  
• Leeto, M., Herbert, D. R., Marillier, R., Schwegmann, A., Fick, L., Brombacher, F. (2006). TH1-Dominant Granulomatous Pathology Does Not Inhibit Fibrosis or Cause Lethality during Murine Schistosomiasis. Am. J. Pathol. 169: 1701-1712 [Abstract] [Full Text]  
• Michels, C., Goyal, P., Nieuwenhuizen, N., Brombacher, F. (2006). Infection with Syphacia obvelata (Pinworm) Induces Protective Th2 Immune Responses and Influences Ovalbumin-Induced Allergic Reactions.. Infect. Immun. 74: 5926-5932 [Abstract] [Full Text]  
• Balic, A., Harcus, Y. M., Taylor, M. D., Brombacher, F., Maizels, R. M. (2006). IL-4R signaling is required to induce IL-10 for the establishment of Th2 dominance. Int Immunol 18: 1421-1431 [Abstract] [Full Text]  
• Holscher, C., Arendse, B., Schwegmann, A., Myburgh, E., Brombacher, F. (2006). Impairment of Alternative Macrophage Activation Delays Cutaneous Leishmaniasis in Nonhealing BALB/c Mice. J. Immunol. 176: 1115-1121 [Abstract] [Full Text]  
• CUTLER, A., BROMBACHER, F. (2005). Cytokine Therapy. Ann. N. Y. Acad. Sci. 1056: 16-29 [Abstract] [Full Text]  
• Arendse, B., Van Snick, J., Brombacher, F. (2005). IL-9 Is a Susceptibility Factor in Leishmania major Infection by Promoting Detrimental Th2/Type 2 Responses. J. Immunol. 174: 2205-2211 [Abstract] [Full Text]  
• Cameron, P., McGachy, A., Anderson, M., Paul, A., Coombs, G. H., Mottram, J. C., Alexander, J., Plevin, R. (2004). Inhibition of Lipopolysaccharide-Induced Macrophage IL-12 Production by Leishmania mexicana Amastigotes: The Role of Cysteine Peptidases and the NF-{kappa}B Signaling Pathway. J. Immunol. 173: 3297-3304 [Abstract] [Full Text]  
• Noben-Trauth, N., Lira, R., Nagase, H., Paul, W. E., Sacks, D. L. (2003). The Relative Contribution of IL-4 Receptor Signaling and IL-10 to Susceptibility to Leishmania major. J. Immunol. 170: 5152-5158 [Abstract] [Full Text]  
• Padigel, U. M., Farrell, J. P. (2003). CD40-CD40 Ligand Costimulation Is Not Required for Initiation and Maintenance of a Th1-Type Response to Leishmania major Infection. Infect. Immun. 71: 1389-1395 [Abstract] [Full Text]  
• Jung, Y.-J., LaCourse, R., Ryan, L., North, R. J. (2002). Evidence Inconsistent with a Negative Influence of T Helper 2 Cells on Protection Afforded by a Dominant T Helper 1 Response against Mycobacterium tuberculosis Lung Infection in Mice. Infect. Immun. 70: 6436-6443 [Abstract] [Full Text]  
• Ritz, S. A., Cundall, M. J., Gajewska, B. U., Alvarez, D., Gutierrez-Ramos, J.-C., Coyle, A. J., McKenzie, A. N. J., Stampfli, M. R., Jordana, M. (2002). Granulocyte Macrophage Colony-Stimulating Factor-Driven Respiratory Mucosal Sensitization Induces Th2 Differentiation and Function Independently of Interleukin-4. Am. J. Respir. Cell Mol. Bio. 27: 428-435 [Abstract] [Full Text]  
• Smeltz, R. B., Chen, J., Ehrhardt, R., Shevach, E. M. (2002). Role of IFN-{gamma} in Th1 Differentiation: IFN-{gamma} Regulates IL-18R{alpha} Expression by Preventing the Negative Effects of IL-4 and by Inducing/Maintaining IL-12 Receptor {beta}2 Expression. J. Immunol. 168: 6165-6172 [Abstract] [Full Text]  
• Yagi, R., Nagai, H., Iigo, Y., Akimoto, T., Arai, T., Kubo, M. (2002). Development of Atopic Dermatitis-Like Skin Lesions in STAT6-Deficient NC/Nga Mice. J. Immunol. 168: 2020-2027 [Abstract] [Full Text]  
• Padigel, U. M., Perrin, P. J., Farrell, J. P. (2001). The Development of a Th1-Type Response and Resistance to Leishmania major Infection in the Absence of CD40-CD40L Costimulation. J. Immunol. 167: 5874-5879 [Abstract] [Full Text]  
• Mountford, A. P., Hogg, K. G., Coulson, P. S., Brombacher, F. (2001). Signaling via Interleukin-4 Receptor {alpha} Chain Is Required for Successful Vaccination against Schistosomiasis in BALB/c Mice. Infect. Immun. 69: 228-236 [Abstract] [Full Text]