We have previously shown decreased expression of the interleukin (IL)-7 receptor α-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.
Received for publication February 8, 2006; accepted May 22, 2006.
From the *Ottawa Health Research Institute, Ottawa, Ontario, Canada; †Division of Infectious Diseases, Ottawa Hospital General Campus, Ottawa, Ontario, Canada; and ‡Departments of Medicine, and Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Supported by grants from the Canadian Institutes for Health Research-Pilot Project Grants for New Investigators, the Canadian Foundation for AIDS Research, and the J.P. Bickell Foundation for Medical Research.
Reprints: Paul MacPherson, MD, PhD, Division of Infectious Diseases, The Ottawa Hospital, General Campus, 501 Smyth Road, Ottawa, Ontario, Canada, K1H 8L6 (e-mail: email@example.com).