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Infection and Immunity, March 2001, p. 1841-1846, Vol. 69, No. 3
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.3.1841-1846.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Critical Role of Cytotoxic T Lymphocytes in Immune Clearance of Rickettsial Infection

David H. Walker,* Juan P. Olano, and Hui-Min Feng

Department of Pathology and WHO Collaborating Center for Tropical Diseases, University of Texas Medical Branch, Galveston, Texas 77555-0609

Received 7 August 2000/Returned for modification 9 September 2000/Accepted 11 December 2000

Cytotoxic T-lymphocyte (CTL) activity developed against the major infected target cells of rickettsial infections, endothelial cells and macrophages. Spleen cells from mice immune to Rickettsia conorii exerted specific major histocompatibility complex (MHC) class I-matched CTL activity against R. conorii-infected SVEC-10 endothelial cells, with peak activity on day 10. Similarly, spleen cells from Rickettsia australis-immune mice exerted specific CTL activity against an R. australis-infected macrophage-like cell line. Gamma interferon (IFN-gamma ) gene knockout mice were more than 100-fold more susceptible to R. australis infection than wild-type C57BL/6 mice. MHC class I gene knockout mice were the most susceptible, more than 50,000-fold more susceptible to a lethal outcome of R. australis infection than wild-type C57BL/6 mice. These results indicate that CTL activity was more critical to recovery from rickettsial infection than were the effects of IFN-gamma . The observation that perforin gene knockout mice were more than 100-fold more susceptible than wild-type C57BL/6 mice indicates that perforin-mediated activity accounts for a large component, but not all, of the CTL-mediated antirickettsial effect. CTL activity was expressed by immune CD8 T lymphocytes. Adoptive transfer of immune CD8 T lymphocytes from IFN-gamma gene knockout mice into R. australis-infected IFN-gamma gene knockout mice dramatically reduced the infectious rickettsial content in the organs, confirming that CD8 T lymphocytes provide immunity against rickettsiae besides that provided by the secretion of IFN-gamma . CTLs appear to be crucial to recovery from rickettsial infection.

* Corresponding author. Mailing address: Department of Pathology, WHO Collaborating Center for Tropical Diseases, 301 University Blvd., Galveston, TX 77555-0609. Phone: (409) 772-2682. Fax: (409) 772-2500. E-mail: dwalker{at}utmb.edu.

Infection and Immunity, March 2001, p. 1841-1846, Vol. 69, No. 3
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.3.1841-1846.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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