Abstract
The production of the T cell lymphokine interleukin-2 (IL-2) was found to impaired in all of seven male patients with AIDS or homosexuals with persistent generalized lymphadenopathy (AIDS related complex, AIDS-RC) whom we studied. Conversely the T cell response to IL-2 was found unimpaired as was the production of the monocyte factor interleukin-1 (IL-1). The response of T cells to IL-1 was found markedly decreased in two of the four patients with AIDS and in two of the three patients with AIDS-RC. Five of six patients had flat curves in autologous mixed lymphocyte cultures with no significant proliferative response throughout 7 days. The exception was a Haitian heterosexual patient with AIDS. Natural killer cell function was decreased in three of four patients with AIDS and two of three patients with AIDS-RC but it augmented normally in the presence of IL-2 in four, including the two who had it normal basally. Responses to pokeweed mitogen were within normal limits in all seven patients despite decreased responses to concanavalin A and phytohaemagglutinin. These findings help pinpoint the defect in AIDS to the T4+ cell, and perhaps even to one of its subpopulations, and suggest a role for IL-2 in the treatment of AIDS.
Full text
PDF







Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Abud-Mendoza C., Alcocer-Varela J., González-Amaro R., Díaz-Jouanen E., Alarcón-Segovia D. Síndrome de inmunodeficiencia adquirida. Datos clínicos y estudios inmunológicos en 9 pacientes vistos en México. Rev Invest Clin. 1984 Oct-Dec;36(4):311–319. [PubMed] [Google Scholar]
- Alcocer-Varela J., Alarcón-Segovia D. Decreased production of and response to interleukin-2 by cultured lymphocytes from patients with systemic lupus erythematosus. J Clin Invest. 1982 Jun;69(6):1388–1392. doi: 10.1172/JCI110579. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Alcocer-Varela J., Laffon A., Alarcón-Segovia D. Defective monocyte production of, and T lymphocyte response to, interleukin-1 in the peripheral blood of patients with systemic lupus erythematosus. Clin Exp Immunol. 1984 Jan;55(1):125–132. [PMC free article] [PubMed] [Google Scholar]
- Ammann A. J., Abrams D., Conant M., Chudwin D., Cowan M., Volberding P., Lewis B., Casavant C. Acquired immune dysfunction in homosexual men: immunologic profiles. Clin Immunol Immunopathol. 1983 Jun;27(3):315–325. doi: 10.1016/0090-1229(83)90084-3. [DOI] [PubMed] [Google Scholar]
- Ben-Zvi A., Mizel S. B., Oppenheim J. J. Generation of human peripheral blood stable E-rosette-forming T cells by interleukin 1. Clin Immunol Immunopathol. 1981 Jun;19(3):330–337. doi: 10.1016/0090-1229(81)90076-3. [DOI] [PubMed] [Google Scholar]
- Farrar J. J., Hilfiker M. L. Antigen-nonspecific helper factors in the antibody response. Fed Proc. 1982 Feb;41(2):263–268. [PubMed] [Google Scholar]
- Farrar J. J., Mizel S. B., Fuller-Farrar J., Farrar W. L., Hilfiker M. L. Macrophage-independent activation of helper T cells. I. Production of Interleukin 2. J Immunol. 1980 Aug;125(2):793–798. [PubMed] [Google Scholar]
- Fishbein E., Alcocer-Varela J., Alarcón-Segovia D. Cellular bases of the production of and response to interleukin-2 in man: role of autologous rosette-forming T-cell subsets defined with monoclonal antibodies. Immunology. 1983 Oct;50(2):223–227. [PMC free article] [PubMed] [Google Scholar]
- Gottlieb M. S., Schroff R., Schanker H. M., Weisman J. D., Fan P. T., Wolf R. A., Saxon A. Pneumocystis carinii pneumonia and mucosal candidiasis in previously healthy homosexual men: evidence of a new acquired cellular immunodeficiency. N Engl J Med. 1981 Dec 10;305(24):1425–1431. doi: 10.1056/NEJM198112103052401. [DOI] [PubMed] [Google Scholar]
- Hauser G. J., Bino T., Rosenberg H., Zakuth V., Geller E., Spirer Z. Interleukin-2 production and response to exogenous interleukin-2 in a patient with the acquired immune deficiency syndrome (AIDS). Clin Exp Immunol. 1984 Apr;56(1):14–17. [PMC free article] [PubMed] [Google Scholar]
- Klatzmann D., Barré-Sinoussi F., Nugeyre M. T., Danquet C., Vilmer E., Griscelli C., Brun-Veziret F., Rouzioux C., Gluckman J. C., Chermann J. C. Selective tropism of lymphadenopathy associated virus (LAV) for helper-inducer T lymphocytes. Science. 1984 Jul 6;225(4657):59–63. doi: 10.1126/science.6328660. [DOI] [PubMed] [Google Scholar]
- Krown S. E., Real F. X., Cunningham-Rundles S., Myskowski P. L., Koziner B., Fein S., Mittelman A., Oettgen H. F., Safai B. Preliminary observations on the effect of recombinant leukocyte A interferon in homosexual men with Kaposi's sarcoma. N Engl J Med. 1983 May 5;308(18):1071–1076. doi: 10.1056/NEJM198305053081806. [DOI] [PubMed] [Google Scholar]
- Laffón A., Alcocer-Varela J., Alarcón-Segovia D. The autologous mixed lymphocyte reaction is not primarily due to xenoantigenic stimulation. Clin Immunol Immunopathol. 1983 Aug;28(2):304–308. doi: 10.1016/0090-1229(83)90164-2. [DOI] [PubMed] [Google Scholar]
- Lane H. C., Masur H., Edgar L. C., Whalen G., Rook A. H., Fauci A. S. Abnormalities of B-cell activation and immunoregulation in patients with the acquired immunodeficiency syndrome. N Engl J Med. 1983 Aug 25;309(8):453–458. doi: 10.1056/NEJM198308253090803. [DOI] [PubMed] [Google Scholar]
- Lifson J. D., Benike C. J., Mark D. F., Koths K., Engleman E. G. Human recombinant interleukin-2 partly reconstitutes deficient in-vitro immune responses of lymphocytes from patients with AIDS. Lancet. 1984 Mar 31;1(8379):698–702. doi: 10.1016/s0140-6736(84)92220-7. [DOI] [PubMed] [Google Scholar]
- Luger T. A., Smolen J. S., Chused T. M., Steinberg A. D., Oppenheim J. J. Human lymphocytes with either the OKT4 or OKT8 phenotype produce interleukin 2 in culture. J Clin Invest. 1982 Aug;70(2):470–473. doi: 10.1172/JCI110637. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mathur-Wagh U., Enlow R. W., Spigland I., Winchester R. J., Sacks H. S., Rorat E., Yancovitz S. R., Klein M. J., William D. C., Mildvan D. Longitudinal study of persistent generalised lymphadenopathy in homosexual men: relation to acquired immunodeficiency syndrome. Lancet. 1984 May 12;1(8385):1033–1038. doi: 10.1016/s0140-6736(84)91449-1. [DOI] [PubMed] [Google Scholar]
- Melendro E. I., Saldate C., Rivero S. J., Alarcon-Segovia D. T-cell subpopulations in the peripheral blood of patients with connective tissue diseases as determined by flow cytometry using monoclonal antibodies. Clin Immunol Immunopathol. 1983 Jun;27(3):340–347. doi: 10.1016/0090-1229(83)90086-7. [DOI] [PubMed] [Google Scholar]
- Meuer S. C., Hussey R. E., Penta A. C., Fitzgerald K. A., Stadler B. M., Schlossman S. F., Reinherz E. L. Cellular origin of interleukin 2 (IL 2) in man: evidence for stimulus-restricted IL 2 production by T4+ and T8+ T lymphocytes. J Immunol. 1982 Sep;129(3):1076–1079. [PubMed] [Google Scholar]
- Mizel S. B. Physicochemical characterization of lymphocyte-activating factor (LAF). J Immunol. 1979 Jun;122(6):2167–2172. [PubMed] [Google Scholar]
- Murray H. W., Rubin B. Y., Masur H., Roberts R. B. Impaired production of lymphokines and immune (gamma) interferon in the acquired immunodeficiency syndrome. N Engl J Med. 1984 Apr 5;310(14):883–889. doi: 10.1056/NEJM198404053101404. [DOI] [PubMed] [Google Scholar]
- Palacios R., Llorente L., Alarcón-Segovia D., Ruíz-Arguelles A., Díaz-Jouanen E. Autologous rosette-forming T cells as the responding cells in human autologous mixed-lymphocyte reaction. J Clin Invest. 1980 Jun;65(6):1527–1530. doi: 10.1172/JCI109819. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rogers M. F., Morens D. M., Stewart J. A., Kaminski R. M., Spira T. J., Feorino P. M., Larsen S. A., Francis D. P., Wilson M., Kaufman L. National case-control study of Kaposi's sarcoma and Pneumocystis carinii pneumonia in homosexual men: Part 2. Laboratory results. Ann Intern Med. 1983 Aug;99(2):151–158. doi: 10.7326/0003-4819-99-2-151. [DOI] [PubMed] [Google Scholar]
- Rook A. H., Masur H., Lane H. C., Frederick W., Kasahara T., Macher A. M., Djeu J. Y., Manischewitz J. F., Jackson L., Fauci A. S. Interleukin-2 enhances the depressed natural killer and cytomegalovirus-specific cytotoxic activities of lymphocytes from patients with the acquired immune deficiency syndrome. J Clin Invest. 1983 Jul;72(1):398–403. doi: 10.1172/JCI110981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rosenberg S. A., Lipsky P. E. The role of monocytes in pokeweed mitogen-stimulated human B cell activation: separate requirements for intact monocytes and a soluble monocyte factor. J Immunol. 1981 Apr;126(4):1341–1345. [PubMed] [Google Scholar]
- Safai B., Sarngadharan M. G., Groopman J. E., Arnett K., Popovic M., Sliski A., Schüpbach J., Gallo R. C. Seroepidemiological studies of human T-lymphotropic retrovirus type III in acquired immunodeficiency syndrome. Lancet. 1984 Jun 30;1(8392):1438–1440. doi: 10.1016/s0140-6736(84)91933-0. [DOI] [PubMed] [Google Scholar]
- Schroff R. W., Gottlieb M. S., Prince H. E., Chai L. L., Fahey J. L. Immunological studies of homosexual men with immunodeficiency and Kaposi's sarcoma. Clin Immunol Immunopathol. 1983 Jun;27(3):300–314. doi: 10.1016/0090-1229(83)90083-1. [DOI] [PubMed] [Google Scholar]
- Shaw J., Caplan B., Paetkau V., Pilarski L. M., Delovitch T. L., McKenzie I. F. Cellular origins of co-stimulator (IL2) and its activity in cytotoxic T lymphocyte responses. J Immunol. 1980 May;124(5):2231–2239. [PubMed] [Google Scholar]
- Sheehy M. J., Quintieri F. B., Leung D. Y., Geha R. S., Dubey D. P., Limmer C. E., Yunis E. J. A human large granular lymphocyte clone with natural killer-like activity and T cell-like surface markers. J Immunol. 1983 Feb;130(2):524–526. [PubMed] [Google Scholar]
- Small C. B., Klein R. S., Friedland G. H., Moll B., Emeson E. E., Spigland I. Community-acquired opportunistic infections and defective cellular immunity in heterosexual drug abusers and homosexual men. Am J Med. 1983 Mar;74(3):433–441. doi: 10.1016/0002-9343(83)90970-1. [DOI] [PubMed] [Google Scholar]
- Solbach W., Barth S., Röllinghoff M., Wagner H. Interactions of human T cell subsets during the induction of cytotoxic T lymphocytes: the role of interleukins. Clin Exp Immunol. 1982 Jul;49(1):167–175. [PMC free article] [PubMed] [Google Scholar]
- Tsuchiya S., Imaizumi M., Minegishi M., Konno T., Tada K. Lack of interleukin-2 production in a patient with OKT4+ T-cell deficiency. N Engl J Med. 1983 May 26;308(21):1294–1294. doi: 10.1056/NEJM198305263082117. [DOI] [PubMed] [Google Scholar]
- Vieira J., Frank E., Spira T. J., Landesman S. H. Acquired immune deficiency in Haitians: opportunistic infections in previously healthy Haitian immigrants. N Engl J Med. 1983 Jan 20;308(3):125–129. doi: 10.1056/NEJM198301203080303. [DOI] [PubMed] [Google Scholar]
- Watson J., Aarden L. A., Shaw J., Paetkau V. Molecular and quantitative analysis of helper T cell-replacing factors on the induction of antigen-sensitive B and T lymphocytes. J Immunol. 1979 May;122(5):1633–1638. [PubMed] [Google Scholar]