Abnormal expression of IL-2R beta (p70)-binding polypeptide on HIV-infected patients' cells.
The constitutively expressed IL-2R beta (p70) chain participates in the formation of high-affinity (h.a.) IL-2R and transduces IL-2-mediated signals to normal cells. Its expression on HIV-infected patients' PBMC was evaluated and was found to be decreased in both nonstimulated CD4+ and CD8+ cells. Mitogenic cell stimulation induced IL-2R beta chain expression on both CD4+ and CD8+ cells from asymptomatic and persistent generalized lymphadenopathy patients but not on those from AIDS patients. Comparison of mean fluorescence intensity of IL-2R beta positively stained cells from normals and patients did not reveal significant differences. Cross-linking of 125I-rIL-2 on patients' PHA-blasts revealed decreased signals corresponding to both IL-2-binding chains and, in some cases, neither IL-2R alpha nor IL-2R beta chains could be detected. Decreased expression of IL-2R beta polypeptide was associated with impaired accumulation of the corresponding mRNA transcripts. Binding experiments with 125I-rIL-2 under h.a. conditions showed a decreased number of IL-2-binding sites/cell which was more pronounced in patients with AIDS than in patients with less advanced clinical stages. In vitro HIV infection of normal PHA-blasts also resulted in a decreased number of h.a. IL-2R/cell. High concentrations of rIL-2 in the absence of other mitogenic stimuli induced a decreased cell proliferation and expression of the IL-2R alpha chain and did not enhance the constitutive NK and the generation of LAK activity in several patients, suggesting an impaired IL-2R beta chain-mediated cell activation.
Sahraoui
Y
Y
Oncogénèse Appliquée, INSERM U268, Hôpital Paul Brousse, Villejuif, France.
Ammar
A
A
Lunardi-Iskandar
Y
Y
Tsapis
A
A
Spanakis
E
E
N'Go
N
N
Allouche
M
M
Bellile
V G
VG
Jasmin
C
C
Georgoulias
V
V
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D005786:Gene Expression Regulation / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis / Q000037:antagonists & inhibitors; D015375:Receptors, Interleukin-2 / Q000037:antagonists & inhibitors / Q000276:immunology*; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D016827:CD8 Antigens; D007376:Interleukin-2; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins