CD8+ T cells specific for immunodominant trans-sialidase epitopes contribute to control of Trypanosoma cruzi infection but are not required for resistance.
CD8(+) T cells are essential for controlling Trypanosoma cruzi infection. During Brazil strain infection, C57BL/6 mice expand parasite-specific CD8(+) T cells recognizing the dominant TSKB20 (ANYKFTLV) and subdominant TSKB74 (VNYDFTLV) trans-sialidase gene (TS)-encoded epitopes with up to 40% of all CD8(+) T cells specific for these epitopes. Although this is one of the largest immunodominant T cell responses described for any infection, most mice fail to clear T. cruzi and subsequently develop chronic disease. To determine if immunodominant TS-specific CD8(+) T cells are necessary for resistance to infection, we epitope-tolerized mice by high-dose i.v. injections of TSKB20 or TSKB74 peptides. Tolerance induction led to deletion of TS-specific CD8(+) T cells but did not prevent the expansion of other effector CD8(+) T cell populations. Mice tolerized against either TSKB20 or TSKB74, or both epitopes simultaneously, exhibited transient increases in parasite loads, although ultimately they controlled the acute infection. Furthermore, BALB/c mice tolerized against the TSKD14 peptide effectively controlled acute T. cruzi infection. These data are consistent with the hypothesis that development of high-frequency CD8(+) T cell populations focused on TS-derived epitopes contributes to optimal control of acute infection but is not required for the development of immune resistance.
Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA 30602, USA.
Charles S
CS
Rosenberg
Dianya L
DL
Martin
Rick L
RL
Tarleton
D000208:Acute Disease; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D014355:Chagas Disease / Q000201:enzymology* / Q000276:immunology* / Q000469:parasitology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D006023:Glycoproteins / Q000276:immunology*; D007108:Immune Tolerance; D007113:Immunity, Innate; D016056:Immunodominant Epitopes / Q000276:immunology*; D008212:Lymphocyte Depletion / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009439:Neuraminidase / Q000276:immunology*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000201:enzymology / Q000276:immunology / Q000469:parasitology
D018984:Epitopes, T-Lymphocyte; D006023:Glycoproteins; D016056:Immunodominant Epitopes; D010446:Peptide Fragments; C069715:trans-sialidase; D009439:Neuraminidase