Selective Priming and Expansion of Antigen-Specific Foxp3−CD4+ T Cells during <i>Listeria monocytogenes</i> Infection

Abstract

The Foxp3-expressing subset of regulatory CD4(+) T cells have defined Ag specificity and play essential roles in maintaining peripheral tolerance by suppressing the activation of self-reactive T cells. Similarly, during chronic infection, pathogen-specific Foxp3-expressing CD4(+) T cells expand and actively suppress pathogen-specific effector T cells. Herein, we used MHC class II tetramers and Foxp3(gfp) knockin mice to track the kinetics and magnitude whereby pathogen-specific Foxp3(+)CD4(+) and Foxp3(-)CD4(+) cells are primed and expand after acute infection with recombinant Listeria monocytogenes (Lm) expressing the non-"self"-Ag 2W1S(52-68). We demonstrate that Lm infection selectively primes proliferation, expansion, and subsequent contraction of Lm-specific Foxp3(-) effector CD4(+) cells, while the numbers of Lm-specific Foxp3(+)CD4(+) regulatory cells remain essentially unchanged. In sharp contrast, purified 2W1S(52-68) peptide primes coordinated expansion of both Foxp3(+) regulatory and Foxp3(-) effector T cells with the same Ag specificity. Taken together, these results indicate selective priming and expansion of Foxp3(-) CD4 T cells is a distinguishing feature for acute bacterial infection.