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Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1988 Mar;71(3):417–422.

Defective T-cell colony formation and IL-2 receptor expression at all stages of HIV infection.

A Winkelstein 1, L A Kingsley 1, R S Klein 1, D W Lyter 1, T L Evans 1, C R Rinaldo Jr 1, L D Weaver 1, L L Machen 1, R C Schadle 1
PMCID: PMC1541669  PMID: 2968201

Abstract

The T-cell colony assay is a highly sensitive measure of immunological dysfunction. The present study evaluated this in vitro response in asymptomatic HIV-infected homosexuals, those with chronic adenopathy as their only clinical manifestation and patients with either ARC or AIDS. The mean colony count in antibody-positive asymptomatic individuals was significantly reduced when compared to either heterosexual controls or antibody-negative homosexuals. Furthermore, there were no differences in the responses of these antibody-positive individuals and those with chronic lymphadenopathy as their only clinical manifestation. By contrast, patients with AIDS or ARC showed a profound defect; this suggests that the colony assay can detect a functional gradient across the spectrum of HIV infections. Colony growth was correlated with the absolute number of T-helper cells and the ability of PHA-stimulated lymphocytes to express IL-2 receptors; no correlation was found with the number of suppressor/cytotoxic cells or in vitro production of IL-2. Recent HIV seroconverters had normal colony counts but impaired ability to express IL-2 receptors. These data suggest a sequential loss of T-cell function as a result of HIV infection; the earliest manifestations are impaired expression of IL-2 receptors and reduced proliferative responses, as measured in the colony assay.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bernstein M. L., Winkelstein A., Dobson S. A. Depressed T cell colony growth in systemic lupus erythematosus. Arthritis Rheum. 1980 Apr;23(4):385–391. doi: 10.1002/art.1780230401. [DOI] [PubMed] [Google Scholar]
  2. Ciobanu N., Welte K., Kruger G., Venuta S., Gold J., Feldman S. P., Wang C. Y., Koziner B., Moore M. A., Safai B. Defective T-cell response to PHA and mitogenic monoclonal antibodies in male homosexuals with acquired immunodeficiency syndrome and its in vitro correction by interleukin 2. J Clin Immunol. 1983 Oct;3(4):332–340. doi: 10.1007/BF00915794. [DOI] [PubMed] [Google Scholar]
  3. Dalgleish A. G., Beverley P. C., Clapham P. R., Crawford D. H., Greaves M. F., Weiss R. A. The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature. 1984 Dec 20;312(5996):763–767. doi: 10.1038/312763a0. [DOI] [PubMed] [Google Scholar]
  4. Fahey J. L., Prince H., Weaver M., Groopman J., Visscher B., Schwartz K., Detels R. Quantitative changes in T helper or T suppressor/cytotoxic lymphocyte subsets that distinguish acquired immune deficiency syndrome from other immune subset disorders. Am J Med. 1984 Jan;76(1):95–100. doi: 10.1016/0002-9343(84)90756-3. [DOI] [PubMed] [Google Scholar]
  5. Fauci A. S., Macher A. M., Longo D. L., Lane H. C., Rook A. H., Masur H., Gelmann E. P. NIH conference. Acquired immunodeficiency syndrome: epidemiologic, clinical, immunologic, and therapeutic considerations. Ann Intern Med. 1984 Jan;100(1):92–106. doi: 10.7326/0003-4819-100-1-92. [DOI] [PubMed] [Google Scholar]
  6. Fishbein D. B., Kaplan J. E., Spira T. J., Miller B., Schonberger L. B., Pinsky P. F., Getchell J. P., Kalyanaraman V. S., Braude J. S. Unexplained lymphadenopathy in homosexual men. A longitudinal study. JAMA. 1985 Aug 16;254(7):930–935. [PubMed] [Google Scholar]
  7. Gupta S., Gillis S., Thornton M., Goldberg M. Autologous mixed lymphocyte reaction in man. XIV. Deficiency of the autologous mixed lymphocyte reaction in acquired immune deficiency syndrome (AIDS) and AIDS related complex (ARC). In vitro effect of purified interleukin-1 and interleukin-2. Clin Exp Immunol. 1984 Nov;58(2):395–401. [PMC free article] [PubMed] [Google Scholar]
  8. 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]
  9. Ioachim H. L., Lerner C. W., Tapper M. L. Lymphadenopathies in homosexual men. Relationships with the acquired immune deficiency syndrome. JAMA. 1983 Sep 9;250(10):1306–1309. doi: 10.1001/jama.250.10.1306. [DOI] [PubMed] [Google Scholar]
  10. Klatzmann D., Champagne E., Chamaret S., Gruest J., Guetard D., Hercend T., Gluckman J. C., Montagnier L. T-lymphocyte T4 molecule behaves as the receptor for human retrovirus LAV. Nature. 1984 Dec 20;312(5996):767–768. doi: 10.1038/312767a0. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Margolick J. B., Volkman D. J., Lane H. C., Fauci A. S. Clonal analysis of T lymphocytes in the acquired immunodeficiency syndrome. Evidence for an abnormality affecting individual helper and suppressor T cells. J Clin Invest. 1985 Aug;76(2):709–715. doi: 10.1172/JCI112025. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. McDougal J. S., Kennedy M. S., Sligh J. M., Cort S. P., Mawle A., Nicholson J. K. Binding of HTLV-III/LAV to T4+ T cells by a complex of the 110K viral protein and the T4 molecule. Science. 1986 Jan 24;231(4736):382–385. doi: 10.1126/science.3001934. [DOI] [PubMed] [Google Scholar]
  15. Metroka C. E., Cunningham-Rundles S., Pollack M. S., Sonnabend J. A., Davis J. M., Gordon B., Fernandez R. D., Mouradian J. Generalized lymphadenopathy in homosexual men. Ann Intern Med. 1983 Nov;99(5):585–591. doi: 10.7326/0003-4819-99-5-585. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Murray J. L., Hersh E. M., Reuben J. M., Munn C. G., Mansell P. W. Abnormal lymphocyte response to exogenous interleukin-2 in homosexuals with acquired immune deficiency syndrome (AIDS) and AIDS related complex (ARC). Clin Exp Immunol. 1985 Apr;60(1):25–30. [PMC free article] [PubMed] [Google Scholar]
  18. Prince H. E., Kermani-Arab V., Fahey J. L. Depressed interleukin 2 receptor expression in acquired immune deficiency and lymphadenopathy syndromes. J Immunol. 1984 Sep;133(3):1313–1317. [PubMed] [Google Scholar]
  19. 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]
  20. 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]
  21. Seligmann M., Chess L., Fahey J. L., Fauci A. S., Lachmann P. J., L'Age-Stehr J., Ngu J., Pinching A. J., Rosen F. S., Spira T. J. AIDS--an immunologic reevaluation. N Engl J Med. 1984 Nov 15;311(20):1286–1292. doi: 10.1056/NEJM198411153112005. [DOI] [PubMed] [Google Scholar]
  22. Siegal F. P., Lopez C., Fitzgerald P. A., Shah K., Baron P., Leiderman I. Z., Imperato D., Landesman S. Opportunistic infections in acquired immune deficiency syndrome result from synergistic defects of both the natural and adaptive components of cellular immunity. J Clin Invest. 1986 Jul;78(1):115–123. doi: 10.1172/JCI112539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Tsang K. Y., Fudenberg H. H., Galbraith G. M., Donnelly R. P., Bishop L. R., Koopmann W. R. Partial restoration of impaired interleukin-2 production and Tac antigen (putative interleukin-2 receptor) expression in patients with acquired immune deficiency syndrome by isoprinosine treatment in vitro. J Clin Invest. 1985 May;75(5):1538–1544. doi: 10.1172/JCI111858. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Winkelstein A. Dependency of human T lymphocyte colony formation on soluble factors produced by accessory or tumor cells. J Immunol. 1983 Jun;130(6):2715–2719. [PubMed] [Google Scholar]
  25. Winkelstein A., Klein R. S., Evans T. L., Dixon B. W., Holder W. L., Weaver L. D. Defective in vitro T cell colony formation in the acquired immunodeficiency syndrome. J Immunol. 1985 Jan;134(1):151–156. [PubMed] [Google Scholar]
  26. Winkelstein A., Simon P. L., Wood D., Machen L. L., Shadduck R. K., Waheed A. The effects of interleukins and other soluble factors on T-lymphocyte colony formation. Immunology. 1986 Jun;58(2):173–177. [PMC free article] [PubMed] [Google Scholar]
  27. Wong-Staal F., Gallo R. C. Human T-lymphotropic retroviruses. Nature. 1985 Oct 3;317(6036):395–403. doi: 10.1038/317395a0. [DOI] [PubMed] [Google Scholar]

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