CD25+CD4+ regulatory T cells and memory T cells prevent lymphopenia-induced proliferation of naive T cells in transient states of lymphopenia.
Lymphopenia has been associated with autoimmune pathology and it has been suggested that lymphopenia-induced proliferation of naive T cells may be responsible for the development of immune pathology. In this study we demonstrate that lymphopenia-induced proliferation is restricted to conditions of extreme lymphopenia, because neither naive nor memory T cells transferred into T cell-depleted hosts proliferate unless the depletion exceeds 90% of the peripheral repertoire. Memory CD4 T cells as well as regulatory CD4 T cells proved to be relatively resistant to depletion regimes, and both subsets restrict the expansion and phenotypic conversion of naive T cells by an IL-7R-dependent mechanism. It therefore seems unlikely that lymphopenia-induced proliferation of peripheral T cells causes deleterious side effects that result in immune pathology in states of partial and transient lymphopenia.
Bourgeois
Christine
C
Division of Molecular Immunology, The National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, U.K.
Stockinger
Brigitta
B
D019264:Adoptive Transfer; D000818:Animals; D015551:Autoimmunity; D015704:CD4 Antigens / Q000378:metabolism; D049109:Cell Proliferation; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism; D007156:Immunologic Memory; D008231:Lymphopenia / Q000276:immunology* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D015375:Receptors, Interleukin-2