Lentivirus infection activates CD4؉ CD25 ؉ T regulatory (Treg) cells. Activation of Treg cells may be due to direct virus infection or chronic antigenic stimulation. Herein we demonstrate that in vitro feline immunodeficiency virus (FIV) infection, but not UV-inactivated virus, activates Treg cells as measured by immunosuppressive function and upregulation of GARP, FoxP3, and membrane-bound transforming growth factor  (TGF-). These data demonstrate for the first time that AIDS lentiviruses infect and activate Treg cells, potentially contributing to immune dysfunction.
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D4ϩ regulatory T cells (Treg cells), currently defined by constitutive expression of the high-affinity interleukin-2 (IL-2) receptor CD25 and the transcription factor Foxp3, play an important role in controlling autoimmune disease and shaping the pathogenesis of viral infections by regulating expansion of T and B effector subsets (1-7). Although Treg cells play an important role in preventing excessive inflammation associated with immune responses to infection, they may in the process prematurely abort protective T and B cell immune responses and allow chronic viremia and more severe pathogenesis. This negative effect of Treg cell activation has been demonstrated in herpesvirus, B and C hepatitis virus, and AIDS lentivirus infections (1, 2, 8-10), supporting the speculation that Treg cells may in part be responsible for the chronic nature of these infections. In the case of the lentiviruses human immunodeficiency virus (HIV) and feline immu- ϩ in vitro infection methods. Purified feline CD4 ϩ CD25 ϩ cells were infected with the NCSU 1 isolate of FIV at an MOI of 2.5. Cells and culture supernatant were harvested at 6 days postinfection and analyzed for virus copy by real-time RT-PCR (A) and p24 antigen (Ag) by ELISA (B). Each bar represents the mean Ϯ standard error of the mean (SEM) of 3 replicates. O.D., optical density. (C) UV inactivation of FIV was confirmed using the FIV-susceptible feline T cell line FCD4-E. Virus was exposed to 1 J of UV light for various times and then added to FCD4-E cells at an MOI of 2. Five cultures per UV inactivation time were observed daily up to 14 days for the formation of syncytia.