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Antigen load and cytokine requirements for CD8 T cell memory generation

Abstract

Memory CD8 T cells are an integral part of protective immunity against viral infections, however the factors controlling memory T cell development are not well understood. In the present study, we provide evidence that antigenic load affects P14 T cell expansion positively, but inversely impacts efficacy to memory conversion during the course of acute LCMV. A gradually shift from a CD62Llo (TEM) phenotype to a CD62Lhi (TCM) phenotype was observed when P14 T cells were introduced on day 3 p.i., while memory T cells from mice that received P14 cells at the same day of viral infection predominately expressed a CD44hiCD62Llo (TEM) phenotype with no alteration in the effector CD8 T cell response for P14+ T cells introduced on Day 0 or Day 3 p.i. We also demonstrate that IL-7 treatment at the contraction phase slightly increases the formation of P14 memory cells when introduced early during the course of the anti-LCMV response (same day of infection). Interestingly, anti-CD127 (anti-IL-7R\[alpha\]) treatment at the contraction phase significantly enhances P14 memory conversion if cells are introduced late during the course of the anti-LCMV response. We addressed that anti-IL-7R \[alpha\] treatment does not increase the activation of antigen-specific CD8⁺ T cells upon in vitro stimulation. Identifying the factors controlling the generation of memory CD8 T cells could result in the development of new strategies for enhancing the memory T cell pool and therefore vaccination design.

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