Feline immunodeficiency virus infection phenotypically and functionally activates immunosuppressive CD4+CD25+ T regulatory cells.
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.
Vahlenkamp
Thomas W
TW
Immunology Program, North Carolina State University, Raleigh, NC 27606, USA.
Tompkins
Mary B
MB
Tompkins
Wayne A F
WA
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000378:metabolism; D000943:Antigens, Differentiation / Q000096:biosynthesis; D000956:Antigens, Viral / Q000096:biosynthesis; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000378:metabolism; D051940:B7-2 Antigen; D060908:CTLA-4 Antigen; D002415:Cats; D002455:Cell Division / Q000276:immunology; D002469:Cell Separation; D002478:Cells, Cultured; D002908:Chronic Disease; D018920:Coculture Techniques; D003208:Concanavalin A / Q000494:pharmacology; D016181:Feline Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology; D007108:Immune Tolerance; D016089:Immunodeficiency Virus, Feline / Q000276:immunology*; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000096:biosynthesis / Q000172:deficiency; D008024:Ligands; D008070:Lipopolysaccharides / Q000494:pharmacology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D018655:Lymphocyte Count; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis* / Q000097:blood / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D015854:Up-Regulation / Q000276:immunology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D000956:Antigens, Viral; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D060908:CTLA-4 Antigen; D007376:Interleukin-2; D008024:Ligands; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D015375:Receptors, Interleukin-2; D003208:Concanavalin A