Transforming growth factor-beta/transforming growth factor-betaRII signaling may regulate CD4+CD25+ T-regulatory cell homeostasis and suppressor function in feline AIDS lentivirus infection.
We have reported that CD4+CD25+ T-regulatory (Treg) cells are fully activated for suppressor function in feline immunodeficiency virus (FIV)-infected cats. Studies have suggested that surface transforming growth factor-beta (TGFbeta; membrane TGFbeta [mTGFbeta]) is a feature of activated CD4+CD25+ Treg cells and may play a role in Treg homeostasis and suppressor function. Herein, we explore the role of TGFbeta in feline Treg homeostasis and suppressor function and what effect FIV infection of cats might have on these processes. Stimulation of CD4+CD25- T helper (Th) cells with Concanavalin A (ConA) plus TGFbeta converts them to Treg-like cells capable of suppressor function. Reverse-transcription polymerase chain reaction and flow cytometry revealed that these ConA/TGFbeta-converted Treg cells upregulate Foxp3 and mTGFbeta. ConA stimulation of CD4+CD25- T cells upregulates TGFbeta receptor II (RII), and pretreatment of these cells with anti-TGFbeta-RII antibodies blocks the TGFbeta-induced conversion to Treg cells. Pretreatment of ConA/TGFbeta-converted Treg cells with anti-TGFbeta antibodies also abrogates their suppressor function, suggesting that Treg homeostasis and suppressor function may be mediated by mTGFbeta. Finally, we show that treatment of CD4+CD25+ mTGFbeta-positive Treg cells from FIV-infected cats with anti-TGFbeta antibodies or treatment of ConA-stimulated CD4+CD25- Th target cells with anti-TGFbeta-RII antibodies diminishes suppressor function. These data suggest that the recruitment of Treg cells from the Th pool and suppressor function of Treg cells are dependent on the TGFbeta/TGFbeta-RII signaling pathway and that this pathway is constitutively upregulated in asymptomatic chronically FIV-infected cats.
Petty
Christopher S
CS
Immunology Program, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA. CSPetty@alumni.ncsu.edu
Tompkins
Mary B
MB
Tompkins
Wayne A
WA
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002415:Cats; D002478:Cells, Cultured; D016181:Feline Acquired Immunodeficiency Syndrome / Q000276:immunology*; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006706:Homeostasis; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D007963:Leukocytes, Mononuclear / Q000276:immunology; D017346:Protein Serine-Threonine Kinases / Q000276:immunology*; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013047:Specific Pathogen-Free Organisms; D016176:T-Lymphocyte Subsets / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000276:immunology*
D053645:Interleukin-2 Receptor alpha Subunit; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II