Skip to main content
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1993 Jun;92(3):448–454. doi: 10.1111/j.1365-2249.1993.tb03419.x

Loss of mucosal CD4 lymphocytes is an early feature of HIV infection.

S G Lim 1, A Condez 1, C A Lee 1, M A Johnson 1, C Elia 1, L W Poulter 1
PMCID: PMC1554790  PMID: 8099858

Abstract

T cell subsets in the gut mucosa are distinct populations and their imbalance in HIV has specific implications in infection. Alterations in T cell subsets in duodenal biopsies were investigated in 17 asymptomatic HIV patients, 24 AIDS patients and 10 controls with non-ulcer dyspepsia. Immunohistochemistry and immunofluorescence using MoAbs to CD3, CD4, CD8, CD68, CD45RA, CD45RO and gp120 were performed on frozen sections. In the lamina propria, there was a significant depletion of CD4+ cells at all stages of HIV, but the density of CD8 lamina propria cells was increased. Intraepithelial lymphocytes were decreased in AIDS patients. There was a significant correlation between cellular density and mucosal CD3+ lymphocytes, and between mucosal CD3+ and CD8+ lymphocytes. Although mucosal CD4,CD45RO+ 'memory' cells were decreased, CD8,CD45RO+ 'memory' cells were increased. Mucosal CD4+ lymphocyte depletion occurred early in HIV, and thus their role in mucosal protection against opportunistic infection should be revised. Mucosal CD8+ lymphocytes initially increased, but decreased when CD4 blood counts were depleted, perhaps contributing to loss of host protection against infection. Intraepithelial lymphocyte depletion may also contribute to opportunistic infection.

Full text

PDF
448

Selected References

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

  1. Batman P. A., Miller A. R., Forster S. M., Harris J. R., Pinching A. J., Griffin G. E. Jejunal enteropathy associated with human immunodeficiency virus infection: quantitative histology. J Clin Pathol. 1989 Mar;42(3):275–281. doi: 10.1136/jcp.42.3.275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bogner J. R., Matuschke A., Heinrich B., Schreiber M. A., Nerl C., Goebel F. D. Expansion of activated T lymphocytes (CD3 + HLA/DR +) detectable in early stages of HIV-1 infection. Klin Wochenschr. 1990 Apr 17;68(8):393–396. doi: 10.1007/BF01648577. [DOI] [PubMed] [Google Scholar]
  3. Budhraja M., Levendoglu H., Kocka F., Mangkornkanok M., Sherer R. Duodenal mucosal T cell subpopulation and bacterial cultures in acquired immune deficiency syndrome. Am J Gastroenterol. 1987 May;82(5):427–431. [PubMed] [Google Scholar]
  4. Chin Y. H., Cai J. P., Hieselaar T. Lymphocyte migration into mucosal lymphoid tissues: mechanism and modulation. Immunol Res. 1991;10(3-4):271–278. doi: 10.1007/BF02919706. [DOI] [PubMed] [Google Scholar]
  5. Crowe S. M., Carlin J. B., Stewart K. I., Lucas C. R., Hoy J. F. Predictive value of CD4 lymphocyte numbers for the development of opportunistic infections and malignancies in HIV-infected persons. J Acquir Immune Defic Syndr. 1991;4(8):770–776. [PubMed] [Google Scholar]
  6. Cummins A. G., LaBrooy J. T., Stanley D. P., Rowland R., Shearman D. J. Quantitative histological study of enteropathy associated with HIV infection. Gut. 1990 Mar;31(3):317–321. doi: 10.1136/gut.31.3.317. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Duijvestijn A., Hamann A. Mechanisms and regulation of lymphocyte migration. Immunol Today. 1989 Jan;10(1):23–28. doi: 10.1016/0167-5699(89)90061-3. [DOI] [PubMed] [Google Scholar]
  8. Fleming S. C., Kapembwa M. S., MacDonald T. T., Griffin G. E. Direct in vitro infection of human intestine with HIV-1. AIDS. 1992 Oct;6(10):1099–1104. doi: 10.1097/00002030-199210000-00006. [DOI] [PubMed] [Google Scholar]
  9. Fox C. H., Kotler D., Tierney A., Wilson C. S., Fauci A. S. Detection of HIV-1 RNA in the lamina propria of patients with AIDS and gastrointestinal disease. J Infect Dis. 1989 Mar;159(3):467–471. doi: 10.1093/infdis/159.3.467. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Gruters R. A., Terpstra F. G., De Goede R. E., Mulder J. W., De Wolf F., Schellekens P. T., Van Lier R. A., Tersmette M., Miedema F. Immunological and virological markers in individuals progressing from seroconversion to AIDS. AIDS. 1991 Jul;5(7):837–844. doi: 10.1097/00002030-199107000-00007. [DOI] [PubMed] [Google Scholar]
  12. Janossy G., Bofill M., Rowe D., Muir J., Beverley P. C. The tissue distribution of T lymphocytes expressing different CD45 polypeptides. Immunology. 1989 Apr;66(4):517–525. [PMC free article] [PubMed] [Google Scholar]
  13. Jarry A., Cortez A., René E., Muzeau F., Brousse N. Infected cells and immune cells in the gastrointestinal tract of AIDS patients. An immunohistochemical study of 127 cases. Histopathology. 1990 Feb;16(2):133–140. doi: 10.1111/j.1365-2559.1990.tb01081.x. [DOI] [PubMed] [Google Scholar]
  14. Kanof M. E., James S. P., Strober W. The phenotype and function of T cells in the lamina propria of the human intestine. Reg Immunol. 1988 Nov-Dec;1(3):190–195. [PubMed] [Google Scholar]
  15. Kotler D. P., Scholes J. V., Tierney A. R. Intestinal plasma cell alterations in acquired immunodeficiency syndrome. Dig Dis Sci. 1987 Feb;32(2):129–138. doi: 10.1007/BF01297100. [DOI] [PubMed] [Google Scholar]
  16. MacDonald T. T., Spencer J. Evidence that activated mucosal T cells play a role in the pathogenesis of enteropathy in human small intestine. J Exp Med. 1988 Apr 1;167(4):1341–1349. doi: 10.1084/jem.167.4.1341. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. Margolick J. B., Volkman D. J., Folks T. M., Fauci A. S. Amplification of HTLV-III/LAV infection by antigen-induced activation of T cells and direct suppression by virus of lymphocyte blastogenic responses. J Immunol. 1987 Mar 15;138(6):1719–1723. [PubMed] [Google Scholar]
  19. Masur H., Ognibene F. P., Yarchoan R., Shelhamer J. H., Baird B. F., Travis W., Suffredini A. F., Deyton L., Kovacs J. A., Falloon J. CD4 counts as predictors of opportunistic pneumonias in human immunodeficiency virus (HIV) infection. Ann Intern Med. 1989 Aug 1;111(3):223–231. doi: 10.7326/0003-4819-111-3-223. [DOI] [PubMed] [Google Scholar]
  20. Mega J., Bruce M. G., Beagley K. W., McGhee J. R., Taguchi T., Pitts A. M., McGhee M. L., Bucy R. P., Eldridge J. H., Mestecky J. Regulation of mucosal responses by CD4+ T lymphocytes: effects of anti-L3T4 treatment on the gastrointestinal immune system. Int Immunol. 1991 Aug;3(8):793–805. doi: 10.1093/intimm/3.8.793. [DOI] [PubMed] [Google Scholar]
  21. Rodgers V. D., Fassett R., Kagnoff M. F. Abnormalities in intestinal mucosal T cells in homosexual populations including those with the lymphadenopathy syndrome and acquired immunodeficiency syndrome. Gastroenterology. 1986 Mar;90(3):552–558. doi: 10.1016/0016-5085(86)91108-x. [DOI] [PubMed] [Google Scholar]
  22. Schnittman S. M., Lane H. C., Greenhouse J., Justement J. S., Baseler M., Fauci A. S. Preferential infection of CD4+ memory T cells by human immunodeficiency virus type 1: evidence for a role in the selective T-cell functional defects observed in infected individuals. Proc Natl Acad Sci U S A. 1990 Aug;87(16):6058–6062. doi: 10.1073/pnas.87.16.6058. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Scott P., Kaufmann S. H. The role of T-cell subsets and cytokines in the regulation of infection. Immunol Today. 1991 Oct;12(10):346–348. doi: 10.1016/0167-5699(91)90063-Y. [DOI] [PubMed] [Google Scholar]
  24. Ullrich R., Zeitz M., Heise W., L'age M., Höffken G., Riecken E. O. Small intestinal structure and function in patients infected with human immunodeficiency virus (HIV): evidence for HIV-induced enteropathy. Ann Intern Med. 1989 Jul 1;111(1):15–21. doi: 10.7326/0003-4819-111-1-15. [DOI] [PubMed] [Google Scholar]
  25. Ullrich R., Zeitz M., Heise W., L'age M., Ziegler K., Bergs C., Riecken E. O. Mucosal atrophy is associated with loss of activated T cells in the duodenal mucosa of human immunodeficiency virus (HIV)-infected patients. Digestion. 1990;46 (Suppl 2):302–307. doi: 10.1159/000200401. [DOI] [PubMed] [Google Scholar]
  26. Vanham G., Kestens L., Penne G., Goilav C., Gigase P., Colebunders R., Vandenbruaene M., Goeman J., van der Groen G., Ceuppens J. L. Subset markers of CD8(+) cells and their relation to enhanced cytotoxic T-cell activity during human immunodeficiency virus infection. J Clin Immunol. 1991 Nov;11(6):345–356. doi: 10.1007/BF00918800. [DOI] [PubMed] [Google Scholar]
  27. Weber J. R., Jr, Dobbins W. O., 3rd The intestinal and rectal epithelial lymphocyte in AIDS. An electron-microscopic study. Am J Surg Pathol. 1986 Sep;10(9):627–639. doi: 10.1097/00000478-198609000-00005. [DOI] [PubMed] [Google Scholar]
  28. Zeitz M., Greene W. C., Peffer N. J., James S. P. Lymphocytes isolated from the intestinal lamina propria of normal nonhuman primates have increased expression of genes associated with T-cell activation. Gastroenterology. 1988 Mar;94(3):647–655. doi: 10.1016/0016-5085(88)90235-1. [DOI] [PubMed] [Google Scholar]
  29. de Martini R. M., Turner R. R., Formenti S. C., Boone D. C., Bishop P. C., Levine A. M., Parker J. W. Peripheral blood mononuclear cell abnormalities and their relationship to clinical course in homosexual men with HIV infection. Clin Immunol Immunopathol. 1988 Feb;46(2):258–271. doi: 10.1016/0090-1229(88)90188-2. [DOI] [PubMed] [Google Scholar]
  30. van Noesel C. J., Gruters R. A., Terpstra F. G., Schellekens P. T., van Lier R. A., Miedema F. Functional and phenotypic evidence for a selective loss of memory T cells in asymptomatic human immunodeficiency virus-infected men. J Clin Invest. 1990 Jul;86(1):293–299. doi: 10.1172/JCI114698. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES