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CD25⁺Foxp3⁺ Regulatory T Cells Facilitate CD4⁺ T Cell Clonal Anergy Induction during the Recovery from Lymphopenia¹

Tracy L. Vanasek^*, Sarada L. Nandiwada^*, Marc K. Jenkins and Daniel L. Mueller^2,*

^* Department of Medicine and Department of Microbiology, and Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455

T cell clonal anergy induction in lymphopenic nu/nu mice was found to be ineffective. Exposure to a tolerizing peptide Ag regimen instead induced aggressive CD4⁺ cell cycle progression and increased Ag responsiveness (priming). Reconstitution of T cell-deficient mice by an adoptive transfer of mature peripheral lymphocytes was accompanied by the development of a CD25⁺Foxp3⁺CTLA-4⁺CD4⁺ regulatory T cell population that acted to dampen Ag-driven cell cycle progression and facilitate the induction of clonal anergy in nearby responder CD25^–CD4⁺ T cells. Thus, an early recovery of CD25⁺ regulatory T cells following a lymphopenic event can prevent exuberant Ag-stimulated CD4⁺ cell cycle progression and promote the development of clonal anergy.

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