CD4+CD25+ Regulatory T Cells are Infected and Activated Phenotypically and Functionally During Acute Infection with Feline Immunodeficiency Virus.

regulatory T cells;FIV

Mexas, Angela Marie ; Gregg A. Dean, Committee Member,Linda Martin, Committee Member,Mary B. Tompkins, Committee Chair,Wayne A. Tompkins, Committee Co-Chair,Mexas, Angela Marie ; Gregg A. Dean ; Committee Member ; Linda Martin ; Committee Member ; Mary B. Tompkins ; Committee Chair ; Wayne A. Tompkins ; Committee Co-Chair

University:North Carolina State University

关键词: regulatory T cells;    FIV;   

Others  :  https://repository.lib.ncsu.edu/bitstream/handle/1840.16/5959/etd.pdf?sequence=1&isAllowed=y

美国|英语

来源: null

【 摘 要 】

HIV-induced AIDS may be mediated by the activation of immunosuppressive CD4+CD25+ T regulatory cells (Tregs). Tregs have been shown to regulate CD4+ and CD8+ immune responses to HIV and FIV antigens in vitro. We tested the hypothesis that Tregs become infected and activated during the acute stage of FIV infection leading to the suppression of CD4+ T helper cell responses.Cats were experimentally infected with FIV-NCSU-1 and blood and lymph node biopsies were collected at 1 week intervals following inoculation.Real-Time PCR was used to determine plasma viremia and relative number of FIV copies in CD4+CD25+ and CD4+CD25- T cell subsets. Flow cytometry was used to assess the absolute numbers of each cell type and the expression of activation markers. Real-time RT-PCR was also used to assess relative increases in FoxP3 and TGF- mRNA levels over time. Treg suppression of IL-2 production in CD4+ T helper cells was assessed by ELISPOT assays and inhibition of cellular proliferation was assessed by incorporation of tritiated thymidine and CFSE. Our results show that peak viremia levels correlate with maximal infectivity in lymph node CD4+CD25+ populations. FIV-gag-mRNA levels are higher in CD4+CD25+ T cells than CD4+CD25- lymph node T cells. Activation of FoxP3 and increased expression of TGF1 in CD4+CD25+ cells correlates with peak plasma viremia and FIV-gag-mRNA levels in CD4+CD25+ T cells. Regulatory function can be detected in CD4+CD25+ T cells during the acute phase of FIV infection. Our findings support the hypothesis that early activation of immunosuppressor function in Treg cells may limit an effective anti-FIV response contributing to the establishment of the chronic infection and the immunodeficiency caused by this virus.