Drug-induced cure drives conversion to a stable and protective CD8+ T central memory response in chronic Chagas disease.
In this study, we document the development of stable, antigen-independent CD8+ T cell memory after drug-induced cure of a chronic infection. By establishing a system for drug cure of chronic Trypanosoma cruzi infection, we present the first extensively documented case of total parasite clearance after drug treatment of this infection. Cure resulted in the emergence of a stable, parasite-specific CD8+ T cell population with the characteristics of central memory cells, based upon expression of CD62L, CCR7, CD127, CD122, Bcl-2 and a reduced immediate in vivo CTL function. CD8+ T cells from treated and cured mice also expanded more rapidly and provided greater protection following challenge than those from chronically infected mice. These results show that complete pathogen clearance results in stable, antigen-independent and protective T cell memory, despite the potentially exhausting effects of prior long-term exposure to antigen in this chronic infection.
Bustamante
Juan M
JM
Center for Tropical and Emerging Global Diseases, Coverdell Center, 500 D.W. Brooks Drive, University of Georgia, Athens, Georgia 30602, USA.
Bixby
Lisa M
LM
Tarleton
Rick L
RL
D000818:Animals; D001973:Bromodeoxyuridine; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D014355:Chagas Disease / Q000188:drug therapy* / Q000276:immunology*; D007156:Immunologic Memory / Q000276:immunology*; D016130:Immunophenotyping; D051379:Mice; D009593:Nitroimidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D019707:Receptors, Chemokine / Q000276:immunology; D016896:Treatment Outcome; D014349:Trypanosoma cruzi / Q000187:drug effects / Q000276:immunology*
D009593:Nitroimidazoles; D019707:Receptors, Chemokine; D001973:Bromodeoxyuridine; C009999:benzonidazole