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.
Rosenberg
Charles S
CS
Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA 30602, USA.
Martin
Dianya L
DL
Tarleton
Rick L
RL
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