Selective priming and expansion of antigen-specific Foxp3 ^-CD4⁺ T cells during Listeria monocytogenes infection

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 Foxp^3gfp 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.