Route of infection determines T helper-1 versus T helper-17 subset differentiation (46.9)

Abstract

Abstract How environmental cues distinctly shape CD4+ T cell differentiation in response to specific bacterial infections remains largely unknown. Here we tested whether the route of infection determined which cytokines were produced by specific memory CD4+ T cells. Listeria monocytogenes and Streptococcus pyogenes were engineered to express the 2W1S antigenic peptide (LM-2W1S and SP-2W1S) and used to infect C57BL/6 mice. Endogenous 2W1S-specific CD4+ T cells were tracked using a 2W1S:I-Ab tetramer and magnetic bead enrichment. Infection with either LM-2W1S or SP-2W1S via the intranasal route resulted in splenic 2W1S:I-Ab-specific CD4+ memory cells that produced interleukin-17A (IL-17A) but not interferon-γ (IFN-γ) upon in vivo challenge, whereas infection with LM-2W1S or SP-2W1S via the intravenous route resulted in splenic 2W1S:I-Ab-specific memory cells that produced IFN-γ, but not IL-17A. These results suggest that the lymphoid environment of primary antigen encounter is an important factor in determining the type of CD4+ T cell memory generated and indicate that the route of immunization should be a major consideration when designing vaccines to improve cell-mediated immunity. This work was funded by the NIH.