CD8 positive T cells influence antigen-specific immune responses through the expression of chemokines.

Abstract

The potential roles of CD8 T-cell-induced chemokines in the expansion of immune responses were examined using DNA immunogen constructs as model antigens. We coimmunized cDNA expression cassettes encoding the -chemokines IL-8 and SDF-1 and the -chemokines MIP-1 , RANTES, and MCP-1 along with DNA immunogens and analyzed the resulting antigen-specific immune responses. In a manner more similar to the traditional immune modulatory role of CD4 T cells via the expression of Th1 or Th2 cytokines, CD8 T cells appeared to play an important role in immune expansion and effector function by producing chemokines. For instance, IL-8 was a strong inducer of CD4 T cells, indicated by strong T helper proliferative responses as well as an enhancement of antibody responses. MIP-1 had a dramatic effect on antibody responses and modulated the shift of immune responses to a Th2-type response. RANTES coimmunization enhanced the levels of antigen-specific Th1 and cytotoxic T lymphocyte (CTL) responses. Among the chemokines examined, MCP-1 was the most potent activator of CD8 CTL activity. The enhanced CTL results are supported by the increased expression of Th1 cytokines IFN- and TNF- and the reduction of IgG1/IgG2a ratio. Our results support that CD8 T cells may expand both humoral and cellular responses in vivo through the elaboration of specific chemokines at the peripheral site of infection during the effector stage of the immune response. (