Identifying third signal cytokines for development of differently functioning CD8 T cells in Mycobacterium tuberculosis infection (70.4)

Abstract

Abstract Mycobacterium tuberculosis (Mtb), causing tuberculosis (TB), is estimated to infect one third of the human population, and kills about 1.8 million people per year. CD8 T cells are the essential components in the adaptive immunity against Mtb. We previously demonstrated that Mtb-specific CD8 T cell populations are divided into two distinct types: either cytotoxic or IFN-γ secreting. However, the third cytokine signals that prime CD8 T cells to evolve into these phenotypes, or to develop capability to have both cytotoxic and IFN-γ producing functions are not known. We found that naïve CD8 T cells adoptively transferred into mice during Mtb infection were primed into more IFN-γ+ IL-2+ TNFα+ and CD107+ IFN-γ+ phenotypes, compared with cells transferred before infection. We also observed dynamic changes in levels of multiple cytokines within tissues over the course of infection. We hypothesize that the relative balances between pro- and anti-inflammatory cytokines contribute to the different phenotypes of CD8 T cells. Here we are using an in vitro OT-I T cell priming system together with lung and lymph node homogenates, as well as individual cytokines identified in those homogenates for effects on CD8 T cell priming and phenotypes. We will also examine the cytokine effects on CD8 T cells in vivo. In summary, our study contributes to a better understanding in how CD8 T cell responses are modulated during Mtb infection, which will help with design of better therapies or vaccines.