Impairment in T-lymphocyte responses during early infection with the human immunodeficiency virus.
Uncertainty has existed as to whether a T-cell deficiency exists in human immunodeficiency virus (HIV) infection different from that inherent in the reduced T-cell numbers characteristic of the disease. Heretofore, methods for measuring T-cell responses in patients have been carried out with systems requiring monocytes as accessory cells. In the presence of high concentrations of interleukin-2, however, highly purified T cells respond in a monocyte-independent fashion to antibody reactive with the CD3 component of the antigen receptor complex Ti/CD3. Highly purified T cells of HIV-infected patients responded subnormally in this anti-CD3/IL-2 system, even in the case of patients who were asymptomatic or had only lymphadenopathy. The defective T-cell responses occurred over a wide range of concentrations of the anti-CD3. Neither poor IL-2 receptor function as reflected by responses to limiting dilutions of IL-2 nor IL-1 receptor function as defined by incremental proliferation when IL-1 is added accounted for this defect, which also correlated poorly with T4 and T8 numbers. These results suggested that the T-cell abnormality was closely related to Ti/CD3 function, was not specifically or restrictively associated with T4 cells, and was not due to defective IL-2- or IL-1-receptor functions. The amount of HIV RNA in 10(5) T lymphocytes from the patients amounted to less than that found in one cell of a standard HIV infected laboratory cell line (CEM), using slot-blot hybridization. Thus the T-cell deficiency we have observed was not likely to be due directly to cell killing by HIV resident in the T4 cells. Other factors may be important in inducing the immunodeficiency, some of which are discussed.
Bentin
J
J
Department of Basic and Clinical Research, Research Institute of Scripps Clinic, La Jolla, California 92037.
Tsoukas
C D
CD
McCutchan
J A
JA
Spector
S A
SA
Richman
D D
DD
Vaughan
J H
JH
D000386:AIDS-Related Complex / Q000276:immunology*; D000911:Antibodies, Monoclonal; D002478:Cells, Cultured; D006679:HIV Seropositivity / Q000276:immunology*; D006716:Homosexuality; D006801:Humans; D008137:Longitudinal Studies; D008199:Lymphadenitis / Q000276:immunology*; D008297:Male; D015375:Receptors, Interleukin-2 / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors
D000911:Antibodies, Monoclonal; D015375:Receptors, Interleukin-2