Feline Immunodeficiency Virus Infection Phenotypically and Functionally Activates Immunosuppressive CD4+CD25+ T Regulatory Cells

Abstract

Disease progression of feline immunodeficiency virus (FIV) infection is characterized by up-regulation of B7.1 and B7.2 costimulatory molecules and their ligand CTLA4 on CD4+ and CD8+ T cells. The CD4+CTLA4+B7+ phenotype described in FIV+ cats is reminiscent of CD4+CD25+CTLA4+ cells, a phenotype described for immunosuppressive T regulatory (Treg) cells. In the present study, we describe the phenotypic and functional characteristics of CD4+CD25+ T cells in PBMC and lymph nodes (LN) of FIV+ and control cats. Similar to Treg cells, feline CD4+CD25+ but not CD4+CD25− T cells directly isolated from LN of FIV+ cats do not produce IL-2 and fail to proliferate in response to mitogen stimulation. Unstimulated CD4+CD25+ T cells from FIV+ cats significantly suppress the proliferative response and the IL-2 production of Con A-stimulated autologous CD4+CD25− T cells compared with unstimulated CD4+CD25+ T cells from FIV− cats. Flow-cytometric analysis confirmed the apparent activation phenotype of the CD4+CD25+ cells in LN of chronically FIV+ cats, because these cells showed significant up-regulation of expression of costimulatory molecules B7.1, B7.2, and CTLA4. These FIV-activated, anergic, immunosuppressive CD25+CTLA4+B7+CD4+ Treg-like cells may contribute to the progressive loss of T cell immune function that is characteristic of FIV infection.