CD25⁺Foxp3⁺ regulatory T cells facilitate CD4 ⁺ T cell clonal anergy induction during the recovery from lymphopenia

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⁺CB4⁺ regulatory T cell population that acted to dampen Ag-driven cell cycle progression and facilitate the induction of clonal anergy in nearby responder CB25 ^-CB4⁺ T cells. Thus, an early recovery of CD25⁺ regulatory T cells following a lympliopenic event can prevent exuberant Ag-stimulated CD4⁺ cell cycle progression and promote the development of clonal anergy.