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 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.
Ertelt
James M
JM
Department of Pediatrics, Center for Infectious Disease and Microbiology Translational Research, University of Minnesota School of Medicine, Minneapolis, MN 55455, USA.
Rowe
Jared H
JH
Johanns
Tanner M
TM
Lai
Joseph C
JC
McLachlan
James B
JB
Way
Sing Sing
SS
D000595:Amino Acid Sequence; D000818:Animals; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics*; D055879:Gene Knock-In Techniques; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D008088:Listeriosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000382:microbiology / Q000473:pathology
D018984:Epitopes, T-Lymphocyte; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D000949:Histocompatibility Antigens Class II