Stable CD8+ T cell memory during persistent Trypanosoma cruzi infection.
CD8(+) T cell responses to persistent infections caused by intracellular pathogens are dominated by resting T effectors and T effector memory cells, with little evidence suggesting that a T central memory (T(CM)) population is generated. Using a model of Trypanosoma cruzi infection, we demonstrate that in contrast to the T effector/T effector memory phenotype of the majority of T. cruzi-specific CD8(+) T cells, a population of cells displaying hallmark characteristics of T(CM) cells is also present during long-term persistent infection. This population expressed the T(CM) marker CD127 and a subset expressed one or more of three other T(CM) markers: CD62L, CCR7, and CD122. Additionally, the majority of CD127(high) cells were KLRG1(low), indicating that they have not been repetitively activated through TCR stimulation. These CD127(high) cells were better maintained than their CD127(low) counterparts following transfer into naive mice, consistent with their observed surface expression of CD127 and CD122, which confer the ability to self-renew in response to IL-7 and IL-15. CD127(high) cells were capable of IFN-gamma production upon peptide restimulation and expanded in response to challenge infection, indicating that these cells are functionally responsive upon Ag re-encounter. These results are in contrast to what is typically observed during many persistent infections and indicate that a stable population of parasite-specific CD8(+) T cells capable of Ag-independent survival is maintained in mice despite the presence of persistent Ag.
Bixby
Lisa M
LM
Center for Tropical and Emerging Global Diseases and Department of Cellular Biology, University of Georgia, Athens, GA 30602, USA.
Tarleton
Rick L
RL
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000469:parasitology* / Q000473:pathology; D049109:Cell Proliferation; D002470:Cell Survival / Q000276:immunology; D014355:Chagas Disease / Q000276:immunology* / Q000469:parasitology; D002908:Chronic Disease; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D007156:Immunologic Memory; D053699:Interleukin-7 Receptor alpha Subunit / Q000096:biosynthesis; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D013997:Time Factors; D014349:Trypanosoma cruzi / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D053699:Interleukin-7 Receptor alpha Subunit