Skip to main content
NCBI home page
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1992 Dec;90(3):376–382. doi: 10.1111/j.1365-2249.1992.tb05854.x

The significance of activation markers on CD8 lymphocytes in human immunodeficiency syndrome: staging and prognostic value.

M Levacher 1, F Hulstaert 1, S Tallet 1, S Ullery 1, J J Pocidalo 1, B A Bach 1
PMCID: PMC1554578  PMID: 1458674

Abstract

The objective of this prospective cohort study was to evaluate the expression of activation markers on CD8 lymphocytes at various clinical stages of HIV infection and to determine the value of these markers in identifying patients likely to have rapidly progressive disease. One hundred and three HIV+ patients, divided into four disease stages, and 34 seronegative controls were evaluated at study entry using flow cytometric immunophenotyping. The HIV patients were followed clinically for disease progression during the following 2 years. CD8 cell numbers and percentage of lymphocytes are increased after HIV infection. Expression of the CD38, HLA-DR and CD57 markers on CD8 cells was significantly increased in asymptomatic HIV-infected patients when compared with controls, as was the CD8 cell population which did not coexpress Leu-8. These activation markers were observed to be further increased in patient groups with more clinically advanced infection. The percentage of CD38 on CD8 cells emerged not only as a discriminator of disease severity, but was a strong predictor of progression in asymptomatic, lymphadenopathy and ARC patients. Given the utility of activation markers on CD8 lymphocytes in staging disease and predicting clinical outcome, the measurement of these parameters should be considered in the monitoring and management of HIV patients.

Full text

PDF
376

Selected References

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

  1. Brinchmann J. E., Gaudernack G., Vartdal F. CD8+ T cells inhibit HIV replication in naturally infected CD4+ T cells. Evidence for a soluble inhibitor. J Immunol. 1990 Apr 15;144(8):2961–2966. [PubMed] [Google Scholar]
  2. Brinchmann J. E., Vartdal F., Thorsby E. T lymphocyte subset changes in human immunodeficiency virus infection. J Acquir Immune Defic Syndr. 1989;2(4):398–403. [PubMed] [Google Scholar]
  3. 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]
  4. Fahey J. L., Taylor J. M., Detels R., Hofmann B., Melmed R., Nishanian P., Giorgi J. V. The prognostic value of cellular and serologic markers in infection with human immunodeficiency virus type 1. N Engl J Med. 1990 Jan 18;322(3):166–172. doi: 10.1056/NEJM199001183220305. [DOI] [PubMed] [Google Scholar]
  5. Fauci A. S., Schnittman S. M., Poli G., Koenig S., Pantaleo G. NIH conference. Immunopathogenic mechanisms in human immunodeficiency virus (HIV) infection. Ann Intern Med. 1991 Apr 15;114(8):678–693. doi: 10.7326/0003-4819-114-8-678. [DOI] [PubMed] [Google Scholar]
  6. Fischl M. A., Richman D. D., Hansen N., Collier A. C., Carey J. T., Para M. F., Hardy W. D., Dolin R., Powderly W. G., Allan J. D. The safety and efficacy of zidovudine (AZT) in the treatment of subjects with mildly symptomatic human immunodeficiency virus type 1 (HIV) infection. A double-blind, placebo-controlled trial. The AIDS Clinical Trials Group. Ann Intern Med. 1990 May 15;112(10):727–737. doi: 10.7326/0003-4819-112-10-727. [DOI] [PubMed] [Google Scholar]
  7. Funaro A., Spagnoli G. C., Ausiello C. M., Alessio M., Roggero S., Delia D., Zaccolo M., Malavasi F. Involvement of the multilineage CD38 molecule in a unique pathway of cell activation and proliferation. J Immunol. 1990 Oct 15;145(8):2390–2396. [PubMed] [Google Scholar]
  8. Giorgi J. V., Detels R. T-cell subset alterations in HIV-infected homosexual men: NIAID Multicenter AIDS cohort study. Clin Immunol Immunopathol. 1989 Jul;52(1):10–18. doi: 10.1016/0090-1229(89)90188-8. [DOI] [PubMed] [Google Scholar]
  9. Giorgi J. V., Nishanian P. G., Schmid I., Hultin L. E., Cheng H. L., Detels R. Selective alterations in immunoregulatory lymphocyte subsets in early HIV (human T-lymphotropic virus type III/lymphadenopathy-associated virus) infection. J Clin Immunol. 1987 Mar;7(2):140–150. doi: 10.1007/BF00916008. [DOI] [PubMed] [Google Scholar]
  10. Gratama J. W., Kluin-Nelemans H. C., Langelaar R. A., den Ottolander G. J., Stijnen T., D'Amaro J., Torensma R., Tanke H. J. Flow cytometric and morphologic studies of HNK1+ (Leu 7+) lymphocytes in relation to cytomegalovirus carrier status. Clin Exp Immunol. 1988 Nov;74(2):190–195. [PMC free article] [PubMed] [Google Scholar]
  11. Gupta S. Abnormality of Leu 2+7+ cells in acquired immune deficiency syndrome (AIDS), AIDS-related complex, and asymptomatic homosexuals. J Clin Immunol. 1986 Nov;6(6):502–509. doi: 10.1007/BF00915256. [DOI] [PubMed] [Google Scholar]
  12. Hercend T., Ritz J., Schlossman S. F., Reinherz E. L. Comparative expression of T9, T10, and Ia antigens on activated human T cell subsets. Hum Immunol. 1981 Nov;3(3):247–259. doi: 10.1016/0198-8859(81)90021-5. [DOI] [PubMed] [Google Scholar]
  13. Jacobson M. A., Bacchetti P., Kolokathis A., Chaisson R. E., Szabo S., Polsky B., Valainis G. T., Mildvan D., Abrams D., Wilber J. Surrogate markers for survival in patients with AIDS and AIDS related complex treated with zidovudine. BMJ. 1991 Jan 12;302(6768):73–78. doi: 10.1136/bmj.302.6768.73. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Ko H. S., Fu S. M., Winchester R. J., Yu D. T., Kunkel H. G. Ia determinants on stimulated human T lymphocytes. Occurrence on mitogen- and antigen-activated T cells. J Exp Med. 1979 Aug 1;150(2):246–255. doi: 10.1084/jem.150.2.246. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lane H. C., Masur H., Gelmann E. P., Longo D. L., Steis R. G., Chused T., Whalen G., Edgar L. C., Fauci A. S. Correlation between immunologic function and clinical subpopulations of patients with the acquired immune deficiency syndrome. Am J Med. 1985 Mar;78(3):417–422. doi: 10.1016/0002-9343(85)90332-8. [DOI] [PubMed] [Google Scholar]
  16. Lang W., Perkins H., Anderson R. E., Royce R., Jewell N., Winkelstein W., Jr Patterns of T lymphocyte changes with human immunodeficiency virus infection: from seroconversion to the development of AIDS. J Acquir Immune Defic Syndr. 1989;2(1):63–69. [PubMed] [Google Scholar]
  17. Levacher M., Tallet S., Dazza M. C., Dournon E., Rouveix B., Pocidalo J. J. T activation marker evaluation in ARC patients treated with AZT. Comparison with CD4+ lymphocyte count in non-progressors and progressors towards AIDS. Clin Exp Immunol. 1990 Aug;81(2):177–182. doi: 10.1111/j.1365-2249.1990.tb03314.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Loken M. R., Brosnan J. M., Bach B. A., Ault K. A. Establishing optimal lymphocyte gates for immunophenotyping by flow cytometry. Cytometry. 1990;11(4):453–459. doi: 10.1002/cyto.990110402. [DOI] [PubMed] [Google Scholar]
  19. Mackewicz C. E., Ortega H. W., Levy J. A. CD8+ cell anti-HIV activity correlates with the clinical state of the infected individual. J Clin Invest. 1991 Apr;87(4):1462–1466. doi: 10.1172/JCI115153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Malone J. L., Simms T. E., Gray G. C., Wagner K. F., Burge J. R., Burke D. S. Sources of variability in repeated T-helper lymphocyte counts from human immunodeficiency virus type 1-infected patients: total lymphocyte count fluctuations and diurnal cycle are important. J Acquir Immune Defic Syndr. 1990;3(2):144–151. [PubMed] [Google Scholar]
  21. Nicholson J. K., McDougal J. S., Spira T. J. Alterations of functional subsets of T helper and T suppressor cell populations in acquired immunodeficiency syndrome (AIDS) and chronic unexplained lymphadenopathy. J Clin Immunol. 1985 Jul;5(4):269–274. doi: 10.1007/BF00929462. [DOI] [PubMed] [Google Scholar]
  22. Phair J., Muñoz A., Detels R., Kaslow R., Rinaldo C., Saah A. The risk of Pneumocystis carinii pneumonia among men infected with human immunodeficiency virus type 1. Multicenter AIDS Cohort Study Group. N Engl J Med. 1990 Jan 18;322(3):161–165. doi: 10.1056/NEJM199001183220304. [DOI] [PubMed] [Google Scholar]
  23. Picker L. J., Terstappen L. W., Rott L. S., Streeter P. R., Stein H., Butcher E. C. Differential expression of homing-associated adhesion molecules by T cell subsets in man. J Immunol. 1990 Nov 15;145(10):3247–3255. [PubMed] [Google Scholar]
  24. Prince H. E., Arens L., Kleinman S. H. CD4 and CD8 subsets defined by dual-color cytofluorometry which distinguish symptomatic from asymptomatic blood donors seropositive for human immunodeficiency virus. Diagn Clin Immunol. 1987;5(4):188–193. [PubMed] [Google Scholar]
  25. Prince H. E., Czaplicki C. D. Preferential loss of Leu 8-, CD45R, HLA-DR+ CD8 cell subsets during in vitro culture of mononuclear cells from human immunodeficiency virus type I (HIV)-seropositive former blood donors. J Clin Immunol. 1989 Sep;9(5):421–428. doi: 10.1007/BF00917108. [DOI] [PubMed] [Google Scholar]
  26. Prince H. E., Jensen E. R. Three-color cytofluorometric analysis of CD8 cell subsets in HIV-1 infection. J Acquir Immune Defic Syndr. 1991;4(12):1227–1232. [PubMed] [Google Scholar]
  27. Prince H. E., Kleinman S., Czaplicki C., John J., Williams A. E. Interrelationships between serologic markers of immune activation and T lymphocyte subsets in HIV infection. J Acquir Immune Defic Syndr. 1990;3(5):525–530. [PubMed] [Google Scholar]
  28. Radka S. F., Charron D. J., Brodsky F. M. Class II molecules of the major histocompatibility complex considered as differentiation markers. Hum Immunol. 1986 Aug;16(4):390–400. doi: 10.1016/0198-8859(86)90065-0. [DOI] [PubMed] [Google Scholar]
  29. Salazar-Gonzalez J. F., Moody D. J., Giorgi J. V., Martinez-Maza O., Mitsuyasu R. T., Fahey J. L. Reduced ecto-5'-nucleotidase activity and enhanced OKT10 and HLA-DR expression on CD8 (T suppressor/cytotoxic) lymphocytes in the acquired immune deficiency syndrome: evidence of CD8 cell immaturity. J Immunol. 1985 Sep;135(3):1778–1785. [PubMed] [Google Scholar]
  30. Taylor J. M., Fahey J. L., Detels R., Giorgi J. V. CD4 percentage, CD4 number, and CD4:CD8 ratio in HIV infection: which to choose and how to use. J Acquir Immune Defic Syndr. 1989;2(2):114–124. [PubMed] [Google Scholar]
  31. Tedder T. F., Penta A. C., Levine H. B., Freedman A. S. Expression of the human leukocyte adhesion molecule, LAM1. Identity with the TQ1 and Leu-8 differentiation antigens. J Immunol. 1990 Jan 15;144(2):532–540. [PubMed] [Google Scholar]
  32. Tomkinson B. E., Wagner D. K., Nelson D. L., Sullivan J. L. Activated lymphocytes during acute Epstein-Barr virus infection. J Immunol. 1987 Dec 1;139(11):3802–3807. [PubMed] [Google Scholar]
  33. Volberding P. A., Lagakos S. W., Koch M. A., Pettinelli C., Myers M. W., Booth D. K., Balfour H. H., Jr, Reichman R. C., Bartlett J. A., Hirsch M. S. Zidovudine in asymptomatic human immunodeficiency virus infection. A controlled trial in persons with fewer than 500 CD4-positive cells per cubic millimeter. The AIDS Clinical Trials Group of the National Institute of Allergy and Infectious Diseases. N Engl J Med. 1990 Apr 5;322(14):941–949. doi: 10.1056/NEJM199004053221401. [DOI] [PubMed] [Google Scholar]
  34. Walker C. M., Moody D. J., Stites D. P., Levy J. A. CD8+ lymphocytes can control HIV infection in vitro by suppressing virus replication. Science. 1986 Dec 19;234(4783):1563–1566. doi: 10.1126/science.2431484. [DOI] [PubMed] [Google Scholar]
  35. Yu D. T., Winchester R. J., Fu S. M., Gibofsky A., Ko H. S., Kunkel H. G. Peripheral blood Ia-positive T cells. Increases in certain diseases and after immunization. J Exp Med. 1980 Jan 1;151(1):91–100. doi: 10.1084/jem.151.1.91. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Zolla-Pazner S., Des Jarlais D. C., Friedman S. R., Spira T. J., Marmor M., Holzman R., Mildvan D., Yancovitz S., Mathur-Wagh U., Garber J. Nonrandom development of immunologic abnormalities after infection with human immunodeficiency virus: implications for immunologic classification of the disease. Proc Natl Acad Sci U S A. 1987 Aug;84(15):5404–5408. doi: 10.1073/pnas.84.15.5404. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. van Es A., Baldwin W. M., Oljans P. J., Tanke H. J., Ploem J. S., van Es L. A. Expression of HLA-DR on T lymphocytes following renal transplantation, and association with graft-rejection episodes and cytomegalovirus infection. Transplantation. 1984 Jan;37(1):65–69. doi: 10.1097/00007890-198401000-00018. [DOI] [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES