Interleukin-7 receptor expression on CD8 T-cells is downregulated by the HIV Tat protein.
We have previously shown decreased expression of the interleukin (IL)-7 receptor alpha-chain (CD127) on CD8 T-cells in HIV-infected patients and an apparent recovery of this receptor in those receiving antiretroviral therapy with sustained viral suppression. Here, we demonstrate that the HIV Tat protein specifically downregulates cell surface expression of CD127 on human CD8 T-cells in a dose- and time-dependent manner. The effects of Tat on CD127 expression could be blocked with anti-Tat monoclonal antibodies or by preincubating Tat with heparin. Tat had no effect on the expression of other cell surface proteins examined, including CD132, or on cell viability over 72 hours. Further, CD127 expression was not altered by other HIV proteins, including gp160 or Nef. Preincubation of purified CD8 T-cells with Tat protein inhibited CD8 T-cell proliferation and perforin synthesis after stimulation with IL-7. Because IL-7 signaling is essential for optimal CD8 T-cell proliferation and function, the downregulation of CD127 and apparent inhibition of cytotoxic activity by Tat may play an important role in HIV-induced immune dysregulation and impaired cell-mediated immunity.
Faller
Elliott M
EM
Ottawa Health Research Institute, Ottawa, Ontario, Canada.
McVey
Mark J
MJ
Kakal
Juzer A
JA
MacPherson
Paul A
PA
D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D015967:Gene Expression Regulation, Viral; D015696:Gene Products, tat / Q000494:pharmacology*; D006678:HIV / Q000235:genetics*; D015851:Interleukin-7 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D020395:Receptors, Interleukin-7 / Q000097:blood / Q000378:metabolism*; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D015851:Interleukin-7; D020395:Receptors, Interleukin-7; D054322:tat Gene Products, Human Immunodeficiency Virus