Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1998 Jan 1;101(1):137–144. doi: 10.1172/JCI195

Contribution of CD4+, CD8+CD28+, and CD8+CD28- T cells to CD3+ lymphocyte homeostasis during the natural course of HIV-1 infection.

A Caruso 1, S Licenziati 1, A D Canaris 1, A Cantalamessa 1, S Fiorentini 1, S Ausenda 1, D Ricotta 1, F Dima 1, F Malacarne 1, A Balsari 1, A Turano 1
PMCID: PMC508549  PMID: 9421475

Abstract

The relationship between the number of circulating CD4+ T cells and the presence of particular CD8+ T cell subsets was analyzed by flow cytometry on PBL from asymptomatic HIV-1-infected patients whose specimens were collected every 2 mo for a total period of 32 mo. Only slight variations were detected in the absolute number of lymphocytes and percentage of CD3+ lymphocytes, whereas both CD4+ and CD8+ T cell subsets showed wide intrapatient variation. Variations in the number of CD8+CD28+ cells paralleled those of the CD4+ T cell subset in each patient tested, while the presence of CD8+CD28- T cells correlated inversely with CD4+ and CD8+CD28+ T cells. These data show that changes in the number of circulating CD4+-and CD8+CD28+ T cells are strongly related to the presence of CD8+CD28- T cells in these patients. Insight into the significance of CD8+CD28- T cell expansion will allow us to understand the mechanisms and significance of the HIV-1- driven change in CD4+CD8+ T cell homeostasis and the basic immunopathology of HIV disease.

Full Text

The Full Text of this article is available as a PDF (250.0 KB).

Selected References

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

  1. Adachi A., Koenig S., Gendelman H. E., Daugherty D., Gattoni-Celli S., Fauci A. S., Martin M. A. Productive, persistent infection of human colorectal cell lines with human immunodeficiency virus. J Virol. 1987 Jan;61(1):209–213. doi: 10.1128/jvi.61.1.209-213.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Adleman L. M., Wofsy D. T-cell homeostasis: implications in HIV infection . J Acquir Immune Defic Syndr. 1993 Feb;6(2):144–152. [PubMed] [Google Scholar]
  3. Amadori A., Zamarchi R., De Silvestro G., Forza G., Cavatton G., Danieli G. A., Clementi M., Chieco-Bianchi L. Genetic control of the CD4/CD8 T-cell ratio in humans. Nat Med. 1995 Dec;1(12):1279–1283. doi: 10.1038/nm1295-1279. [DOI] [PubMed] [Google Scholar]
  4. Azuma M., Phillips J. H., Lanier L. L. CD28- T lymphocytes. Antigenic and functional properties. J Immunol. 1993 Feb 15;150(4):1147–1159. [PubMed] [Google Scholar]
  5. Balk S. P., Ebert E. C., Blumenthal R. L., McDermott F. V., Wucherpfennig K. W., Landau S. B., Blumberg R. S. Oligoclonal expansion and CD1 recognition by human intestinal intraepithelial lymphocytes. Science. 1991 Sep 20;253(5026):1411–1415. doi: 10.1126/science.1716785. [DOI] [PubMed] [Google Scholar]
  6. Barnett S. W., Barboza A., Wilcox C. M., Forsmark C. E., Levy J. A. Characterization of human immunodeficiency virus type 1 strains recovered from the bowel of infected individuals. Virology. 1991 Jun;182(2):802–809. doi: 10.1016/0042-6822(91)90621-h. [DOI] [PubMed] [Google Scholar]
  7. Blumberg R. S., Yockey C. E., Gross G. G., Ebert E. C., Balk S. P. Human intestinal intraepithelial lymphocytes are derived from a limited number of T cell clones that utilize multiple V beta T cell receptor genes. J Immunol. 1993 Jun 1;150(11):5144–5153. [PubMed] [Google Scholar]
  8. Boll G., Reimann J. Lamina propria T cell subsets in the small and large intestine of euthymic and athymic mice. Scand J Immunol. 1995 Aug;42(2):191–201. doi: 10.1111/j.1365-3083.1995.tb03645.x. [DOI] [PubMed] [Google Scholar]
  9. Borthwick N. J., Bofill M., Gombert W. M., Akbar A. N., Medina E., Sagawa K., Lipman M. C., Johnson M. A., Janossy G. Lymphocyte activation in HIV-1 infection. II. Functional defects of CD28- T cells. AIDS. 1994 Apr;8(4):431–441. doi: 10.1097/00002030-199404000-00004. [DOI] [PubMed] [Google Scholar]
  10. Borthwick N. J., Bofill M., Hassan I., Panayiotidis P., Janossy G., Salmon M., Akbar A. N. Factors that influence activated CD8+ T-cell apoptosis in patients with acute herpesvirus infections: loss of costimulatory molecules CD28, CD5 and CD6 but relative maintenance of Bax and Bcl-X expression. Immunology. 1996 Aug;88(4):508–515. [PMC free article] [PubMed] [Google Scholar]
  11. Brinchmann J. E., Dobloug J. H., Heger B. H., Haaheim L. L., Sannes M., Egeland T. Expression of costimulatory molecule CD28 on T cells in human immunodeficiency virus type 1 infection: functional and clinical correlations. J Infect Dis. 1994 Apr;169(4):730–738. doi: 10.1093/infdis/169.4.730. [DOI] [PubMed] [Google Scholar]
  12. Caruso A., Cantalamessa A., Licenziati S., Peroni L., Prati E., Martinelli F., Canaris A. D., Folghera S., Gorla R., Balsari A. Expression of CD28 on CD8+ and CD4+ lymphocytes during HIV infection. Scand J Immunol. 1994 Nov;40(5):485–490. doi: 10.1111/j.1365-3083.1994.tb03494.x. [DOI] [PubMed] [Google Scholar]
  13. Clegg C. H., Rulffes J. T., Wallace P. M., Haugen H. S. Regulation of an extrathymic T-cell development pathway by oncostatin M. Nature. 1996 Nov 21;384(6606):261–263. doi: 10.1038/384261a0. [DOI] [PubMed] [Google Scholar]
  14. Crawford D. H., Brickell P., Tidman N., McConnell I., Hoffbrand A. V., Janossy G. Increased numbers of cells with suppressor T cell phenotype in the peripheral blood of patients with infectious mononucleosis. Clin Exp Immunol. 1981 Feb;43(2):291–297. [PMC free article] [PubMed] [Google Scholar]
  15. Dalod M., Fiorentino S., Delamare C., Rouzioux C., Sicard D., Guillet J. G., Gomard E. Delayed virus-specific CD8+ cytotoxic T lymphocyte activity in an HIV-infected individual with high CD4+ cell counts: correlations with various parameters of disease progression. AIDS Res Hum Retroviruses. 1996 Apr 10;12(6):497–506. doi: 10.1089/aid.1996.12.497. [DOI] [PubMed] [Google Scholar]
  16. Ebert E. C. Proliferative responses of human intraepithelial lymphocytes to various T-cell stimuli. Gastroenterology. 1989 Dec;97(6):1372–1381. doi: 10.1016/0016-5085(89)90379-x. [DOI] [PubMed] [Google Scholar]
  17. Fagnoni F. F., Vescovini R., Mazzola M., Bologna G., Nigro E., Lavagetto G., Franceschi C., Passeri M., Sansoni P. Expansion of cytotoxic CD8+ CD28- T cells in healthy ageing people, including centenarians. Immunology. 1996 Aug;88(4):501–507. doi: 10.1046/j.1365-2567.1996.d01-689.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Fantini J., Yahi N., Chermann J. C. Human immunodeficiency virus can infect the apical and basolateral surfaces of human colonic epithelial cells. Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):9297–9301. doi: 10.1073/pnas.88.20.9297. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Fiorentino S., Dalod M., Olive D., Guillet J. G., Gomard E. Predominant involvement of CD8+CD28- lymphocytes in human immunodeficiency virus-specific cytotoxic activity. J Virol. 1996 Mar;70(3):2022–2026. doi: 10.1128/jvi.70.3.2022-2026.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Franceschi C., Monti D., Sansoni P., Cossarizza A. The immunology of exceptional individuals: the lesson of centenarians. Immunol Today. 1995 Jan;16(1):12–16. doi: 10.1016/0167-5699(95)80064-6. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Ho D. D., Neumann A. U., Perelson A. S., Chen W., Leonard J. M., Markowitz M. Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature. 1995 Jan 12;373(6510):123–126. doi: 10.1038/373123a0. [DOI] [PubMed] [Google Scholar]
  23. Ho H. N., Hultin L. E., Mitsuyasu R. T., Matud J. L., Hausner M. A., Bockstoce D., Chou C. C., O'Rourke S., Taylor J. M., Giorgi J. V. Circulating HIV-specific CD8+ cytotoxic T cells express CD38 and HLA-DR antigens. J Immunol. 1993 Apr 1;150(7):3070–3079. [PubMed] [Google Scholar]
  24. Jondal M., Klein G. Surface markers on human B and T lymphocytes. II. Presence of Epstein-Barr virus receptors on B lymphocytes. J Exp Med. 1973 Dec 1;138(6):1365–1378. doi: 10.1084/jem.138.6.1365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Labalette M., Salez F., Pruvot F. R., Noel C., Dessaint J. P. CD8 lymphocytosis in primary cytomegalovirus (CMV) infection of allograft recipients: expansion of an uncommon CD8+ CD57- subset and its progressive replacement by CD8+ CD57+ T cells. Clin Exp Immunol. 1994 Mar;95(3):465–471. doi: 10.1111/j.1365-2249.1994.tb07020.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Maher P., O'Toole C. M., Wreghitt T. G., Spiegelhalter D. J., English T. A. Cytomegalovirus infection in cardiac transplant recipients associated with chronic T cell subset ratio inversion with expansion of a Leu-7+ TS-C+ subset. Clin Exp Immunol. 1985 Dec;62(3):515–524. [PMC free article] [PubMed] [Google Scholar]
  27. Margolick J. B., Muñoz A., Donnenberg A. D., Park L. P., Galai N., Giorgi J. V., O'Gorman M. R., Ferbas J. Failure of T-cell homeostasis preceding AIDS in HIV-1 infection. The Multicenter AIDS Cohort Study. Nat Med. 1995 Jul;1(7):674–680. doi: 10.1038/nm0795-674. [DOI] [PubMed] [Google Scholar]
  28. McFarland H. I., Nahill S. R., Maciaszek J. W., Welsh R. M. CD11b (Mac-1): a marker for CD8+ cytotoxic T cell activation and memory in virus infection. J Immunol. 1992 Aug 15;149(4):1326–1333. [PubMed] [Google Scholar]
  29. Menitove J. E., Aster R. H., Casper J. T., Lauer S. J., Gottschall J. L., Williams J. E., Gill J. C., Wheeler D. V., Piaskowski V., Kirchner P. T-lymphocyte subpopulations in patients with classic hemophilia treated with cryoprecipitate and lyophilized concentrates. N Engl J Med. 1983 Jan 13;308(2):83–86. doi: 10.1056/NEJM198301133080206. [DOI] [PubMed] [Google Scholar]
  30. Mosmann T. R., Cherwinski H., Bond M. W., Giedlin M. A., Coffman R. L. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol. 1986 Apr 1;136(7):2348–2357. [PubMed] [Google Scholar]
  31. Nicholson J. K., Jones B. M., Hubbard M. CD4 T-lymphocyte determinations on whole blood specimens using a single-tube three-color assay. Cytometry. 1993;14(6):685–689. doi: 10.1002/cyto.990140614. [DOI] [PubMed] [Google Scholar]
  32. Pattengale P. K., Smith R. W., Gerber P. Selective transformation of B lymphocytes by E.B. virus. Lancet. 1973 Jul 14;2(7820):93–94. doi: 10.1016/s0140-6736(73)93286-8. [DOI] [PubMed] [Google Scholar]
  33. Posnett D. N., Sinha R., Kabak S., Russo C. Clonal populations of T cells in normal elderly humans: the T cell equivalent to "benign monoclonal gammapathy". J Exp Med. 1994 Feb 1;179(2):609–618. doi: 10.1084/jem.179.2.609. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Reinherz E. L., O'Brien C., Rosenthal P., Schlossman S. F. The cellular basis for viral-induced immunodeficiency: analysis by monoclonal antibodies. J Immunol. 1980 Sep;125(3):1269–1274. [PubMed] [Google Scholar]
  35. Reusser P., Riddell S. R., Meyers J. D., Greenberg P. D. Cytotoxic T-lymphocyte response to cytomegalovirus after human allogeneic bone marrow transplantation: pattern of recovery and correlation with cytomegalovirus infection and disease. Blood. 1991 Sep 1;78(5):1373–1380. [PubMed] [Google Scholar]
  36. Roederer M. T-cell dynamics of immunodeficiency. Nat Med. 1995 Jul;1(7):621–622. doi: 10.1038/nm0795-621. [DOI] [PubMed] [Google Scholar]
  37. Romagnani S. Human TH1 and TH2 subsets: doubt no more. Immunol Today. 1991 Aug;12(8):256–257. doi: 10.1016/0167-5699(91)90120-I. [DOI] [PubMed] [Google Scholar]
  38. Rothstein G. Hematopoiesis in the aged: a model of hematopoietic dysregulation? Blood. 1993 Nov 1;82(9):2601–2604. [PubMed] [Google Scholar]
  39. Sarnacki S., Bègue B., Buc H., Le Deist F., Cerf-Bensussan N. Enhancement of CD3-induced activation of human intestinal intraepithelial lymphocytes by stimulation of the beta 7-containing integrin defined by HML-1 monoclonal antibody. Eur J Immunol. 1992 Nov;22(11):2887–2892. doi: 10.1002/eji.1830221120. [DOI] [PubMed] [Google Scholar]
  40. Van Kerckhove C., Russell G. J., Deusch K., Reich K., Bhan A. K., DerSimonian H., Brenner M. B. Oligoclonality of human intestinal intraepithelial T cells. J Exp Med. 1992 Jan 1;175(1):57–63. doi: 10.1084/jem.175.1.57. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Vingerhoets J. H., Vanham G. L., Kestens L. L., Penne G. G., Colebunders R. L., Vandenbruaene M. J., Goeman J., Gigase P. L., De Boer M., Ceuppens J. L. Increased cytolytic T lymphocyte activity and decreased B7 responsiveness are associated with CD28 down-regulation on CD8+ T cells from HIV-infected subjects. Clin Exp Immunol. 1995 Jun;100(3):425–433. doi: 10.1111/j.1365-2249.1995.tb03717.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Wei X., Ghosh S. K., Taylor M. E., Johnson V. A., Emini E. A., Deutsch P., Lifson J. D., Bonhoeffer S., Nowak M. A., Hahn B. H. Viral dynamics in human immunodeficiency virus type 1 infection. Nature. 1995 Jan 12;373(6510):117–122. doi: 10.1038/373117a0. [DOI] [PubMed] [Google Scholar]
  43. Zander A. R., Reuben J. M., Johnston D., Vellekoop L., Dicke K. A., Yau J. C., Hersh E. M. Immune recovery following allogeneic bone marrow transplantation. Transplantation. 1985 Aug;40(2):177–183. doi: 10.1097/00007890-198508000-00014. [DOI] [PubMed] [Google Scholar]
  44. Zheng B., Han S., Zhu Q., Goldsby R., Kelsoe G. Alternative pathways for the selection of antigen-specific peripheral T cells. Nature. 1996 Nov 21;384(6606):263–266. doi: 10.1038/384263a0. [DOI] [PubMed] [Google Scholar]
  45. van den Berg A. P., van Son W. J., Janssen R. A., Brons N. H., Heyn A. A., Scholten-Sampson A., Postma S., van der Giessen M., Tegzess A. M., de Leij L. H. Recovery from cytomegalovirus infection is associated with activation of peripheral blood lymphocytes. J Infect Dis. 1992 Dec;166(6):1228–1235. doi: 10.1093/infdis/166.6.1228. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES