IL2-R alpha chain inhibitory factor (p29) produced by HIV-infected macrophages: cell target and mode of action.
We recently reported that HIV-infected adherent cells spontaneously produce a 29-kDa protein (p29), most probably of nonviral origin, which inhibits expression of the IL2R alpha chain on activated normal T cells. Studying the mode of action of this molecule, we observed that monocyte depletion of normal PBMC either by plastic adherence or by complement-mediated cytotoxicity using macrophage-specific monoclonal antibodies abrogated the inhibitory effect of p29. The biological activity of p29 in adherent cell-depleted PBMC could be restored either with rIL1 or with as little as 10(5) autologous adherent cells/ml. Moreover, p29 could not inhibit IL1 biologic activity, nor its binding to IL1 receptor. In addition, p29 could not inhibit the production of IL1 and TNF alpha by normal adherent cells. Positive and negative cell sorting of normal T cells as well as two-color immunofluorescence studies revealed that CD8+ subsets are the main cell targets of p29, which also mediated an impaired generation of alloantigen-specific CTL. Conversely, only a slight inhibitory activity could be detected in highly purified CD4+ cells. Our findings suggest that HIV-induced production of p29 inhibitory factor by adherent cells may be involved in mechanisms responsible for some of the impaired cytotoxic functions observed in AIDS patients.
Ammar
A
A
Oncogenese Appliquee, INSERM U268, Hôpital Paul Brousse, Villejuif, France.
Bertoli
A M
AM
Chouaib
S
S
Clemenceau
C
C
Jasmin
C
C
Georgoulias
V
V
D016827:CD8 Antigens; D002448:Cell Adhesion / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology; D007519:Isoantigens / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis*; D012191:Retroviridae Proteins / Q000502:physiology*; D013491:Suppressor Factors, Immunologic / Q000502:physiology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D016827:CD8 Antigens; C075749:HIV-infected adherent cell-derived inhibitory factor, p29; D007375:Interleukin-1; D007519:Isoantigens; D015375:Receptors, Interleukin-2; D012191:Retroviridae Proteins; D013491:Suppressor Factors, Immunologic