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Stable CD8⁺ T Cell Memory during Persistent Trypanosoma cruzi Infection¹

Center for Tropical and Emerging Global Diseases and Department of Cellular Biology, University of Georgia, Athens, GA 30602

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- 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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Research Grants AI-022070 and AI-033106 (to R.L.T.).

² Address correspondence and reprint requests to Dr. Rick L. Tarleton, Center for Tropical and Emerging Global Diseases, 310 Coverdell Center, 500 D.W. Brooks Drive, University of Georgia, Athens, GA 30602. E-mail address: Tarleton{at}cb.uga.edu

³ Abbreviations used in this paper: T_CM, T central memory; T_E, T effector; T_EM, T effector memory; TCT, tissue culture trypomastigote; SC, spleen cell; CRZP, cruzipain; GFT, β-galactofuranosyltransferase; FMO, fluorescence minus one.

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