Production of a tac inhibitory activity by adherent cells of HIV-infected subjects at different clinical stages.
Studying the mechanisms of the impaired T-cell colony growth from HIV-infected subjects, we have demonstrated that depletion of adherent cells from some patients' peripheral blood mononuclear cells enhanced the plating efficiency of T colony-forming cells. We report here that media conditioned by patients' cells but not normal adherent cells could inhibit the expression of the interleukin-2 receptor alpha (IL-2R alpha) chain but not the IL-2R beta chain in a dose-dependent manner. This inhibitory activity was produced by macrophage-monocyte cells since they displayed the My9+ My7+ OKM1+ phenotype and since adherent cell depletion by complement-mediated cytotoxicity with the My9 monoclonal antibody completely abrogated production of the inhibitory activity. A similar inhibitory activity, which could not be recognized by anti-p24 or anti-gp 120 monoclonal antibody or purified human anti-HIV immun]gobulin G in Western blot assays, could also be detected in culture supernatants of in vitro HIV-infected normal adherent and U937 leukemic cells. Production of IL-2R alpha chain inhibitory activity was associated with a decreased mitogen-induced expression of IL-2R alpha chain on patients' PBMC in 8 of 10 studied cases. Its production could be detected in 82, 58, and 91% of media conditioned by adherent cells from stage II, III, and IV patients, respectively. The amount of IL-2R alpha chain inhibitor released by patients' adherent cells increased during the deterioration of the patients' clinical status, and zidovudine treatment completely abrogated its production in all patients. These findings strongly suggest that production of IL-2R alpha chain inhibitory activity is involved in the pathophysiology of the impaired T-cell responses during HIV infection and could be of clinical relevance during the patients' follow-up.
Ammar
A
A
Unité d'Oncogénése Appliquée, INSERM U268, Hôpital Paul Brousse, Villejuif, France.
Bertoli
A M
AM
Sahraoui
Y
Y
Perraki
M
M
Tsilivakos
V
V
Meyer
P
P
Rozenbaum
W
W
Jasmin
C
C
Georgoulias
V
V
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000276:immunology*; D002462:Cell Membrane / Q000276:immunology; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D015375:Receptors, Interleukin-2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D015215:Zidovudine / Q000627:therapeutic use
D015375:Receptors, Interleukin-2; D015215:Zidovudine