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. 1995 Oct;37(4):524–529. doi: 10.1136/gut.37.4.524

Loss of CD4 T lymphocytes in patients infected with human immunodeficiency virus type 1 is more pronounced in the duodenal mucosa than in the peripheral blood. Berlin Diarrhea/Wasting Syndrome Study Group.

T Schneider 1, H U Jahn 1, W Schmidt 1, E O Riecken 1, M Zeitz 1, R Ullrich 1
PMCID: PMC1382905  PMID: 7489940

Abstract

Although changes in T lymphocyte subset distribution in the peripheral blood of patients infected with human immunodeficiency virus (HIV) are well defined it is not known whether these changes reflect changes in lymphoid compartments clearly involved in HIV related disease like the intestinal mucosa. This study analysed lymphocytes isolated simultaneously from the peripheral blood and duodenal biopsy specimens by three colour flow cytometry in eight asymptomatic HIV infected patients, 26 AIDS patients, and 23 controls. The proportion of CD4, CD8, CD4-CD8-, or gamma delta T cells did not correlate between circulating and duodenal T cells. CD4 T cells were reduced in the peripheral blood (7.5% (25th-75th percentile, 2-16%) v 52% (41-63%), p < 0.0005) and even more reduced in the duodenum (1% (1-2%) v 36% (23-57%), p < 0.0005) of AIDS patients compared with controls. Patients with asymptomatic HIV infection had intermediate CD4 T cells in the peripheral blood (24% (22-35%); p < 0.002 v controls; p < 0.01 v AIDS) but like AIDS patients very low CD4 T cells in the duodenum (3% (1-6%); p < 0.002 v controls). The ratio of duodenal to circulating CD4+ T cells was significantly reduced to 0.2 (0-1) in AIDS patients (p < 0.001) and even to 0.1 (0.04-0.5) in asymptomatic HIV infected patients (p < 0.002) compared with 0.72 (0.44-0.95) in controls. These findings show an early and preferential loss of duodenal CD4 T cells in HIV infection. Immunological abnormalities in HIV infection are distinct between lymphoid compartments, and profound immunodeficiency may occur in the intestinal immune system although circulating T cells are largely preserved.

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Selected References

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  1. Baltimore D., Feinberg M. B. HIV revealed: toward a natural history of the infection. N Engl J Med. 1989 Dec 14;321(24):1673–1675. doi: 10.1056/NEJM198912143212409. [DOI] [PubMed] [Google Scholar]
  2. Bass H. Z., Nishanian P., Hardy W. D., Mitsuyasu R. T., Esmail E., Cumberland W., Fahey J. L. Immune changes in HIV-1 infection: significant correlations and differences in serum markers and lymphoid phenotypic antigens. Clin Immunol Immunopathol. 1992 Jul;64(1):63–70. doi: 10.1016/0090-1229(92)90060-2. [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. Burcham J., Marmor M., Dubin N., Tindall B., Cooper D. A., Berry G., Penny R. CD4% is the best predictor of development of AIDS in a cohort of HIV-infected homosexual men. AIDS. 1991 Apr;5(4):365–372. doi: 10.1097/00002030-199104000-00002. [DOI] [PubMed] [Google Scholar]
  5. Ellakany S., Whiteside T. L., Schade R. R., van Thiel D. H. Analysis of intestinal lymphocyte subpopulations in patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. Am J Clin Pathol. 1987 Mar;87(3):356–364. doi: 10.1093/ajcp/87.3.356. [DOI] [PubMed] [Google Scholar]
  6. Embretson J., Zupancic M., Ribas J. L., Burke A., Racz P., Tenner-Racz K., Haase A. T. Massive covert infection of helper T lymphocytes and macrophages by HIV during the incubation period of AIDS. Nature. 1993 Mar 25;362(6418):359–362. doi: 10.1038/362359a0. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Ho D. D., Moudgil T., Alam M. Quantitation of human immunodeficiency virus type 1 in the blood of infected persons. N Engl J Med. 1989 Dec 14;321(24):1621–1625. doi: 10.1056/NEJM198912143212401. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Kotler D. P., Reka S., Borcich A., Cronin W. J. Detection, localization, and quantitation of HIV-associated antigens in intestinal biopsies from patients with HIV. Am J Pathol. 1991 Oct;139(4):823–830. [PMC free article] [PubMed] [Google Scholar]
  11. Lim S. G., Condez A., Lee C. A., Johnson M. A., Elia C., Poulter L. W. Loss of mucosal CD4 lymphocytes is an early feature of HIV infection. Clin Exp Immunol. 1993 Jun;92(3):448–454. doi: 10.1111/j.1365-2249.1993.tb03419.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. McCune J. M. HIV-1: the infective process in vivo. Cell. 1991 Jan 25;64(2):351–363. doi: 10.1016/0092-8674(91)90644-e. [DOI] [PubMed] [Google Scholar]
  14. Nabel G., Baltimore D. An inducible transcription factor activates expression of human immunodeficiency virus in T cells. Nature. 1987 Apr 16;326(6114):711–713. doi: 10.1038/326711a0. [DOI] [PubMed] [Google Scholar]
  15. Pantaleo G., Graziosi C., Butini L., Pizzo P. A., Schnittman S. M., Kotler D. P., Fauci A. S. Lymphoid organs function as major reservoirs for human immunodeficiency virus. Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9838–9842. doi: 10.1073/pnas.88.21.9838. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Pantaleo G., Graziosi C., Demarest J. F., Butini L., Montroni M., Fox C. H., Orenstein J. M., Kotler D. P., Fauci A. S. HIV infection is active and progressive in lymphoid tissue during the clinically latent stage of disease. Nature. 1993 Mar 25;362(6418):355–358. doi: 10.1038/362355a0. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. Schieferdecker H. L., Ullrich R., Hirseland H., Zeitz M. T cell differentiation antigens on lymphocytes in the human intestinal lamina propria. J Immunol. 1992 Oct 15;149(8):2816–2822. [PubMed] [Google Scholar]
  19. Schneider T., Hildebrandt P., Rokos K., Schubert U., Rönspeck W., Grund C., Beck A., Blesken R., Kulins G., Oldenburg H. Expression of nef, vpu, CA and CD4 during the infection of lymphoid and monocytic cell lines with HIV-1. Arch Virol. 1992;125(1-4):161–176. doi: 10.1007/BF01309635. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Ullrich R., Schieferdecker H. L., Ziegler K., Riecken E. O., Zeitz M. gamma delta T cells in the human intestine express surface markers of activation and are preferentially located in the epithelium. Cell Immunol. 1990 Jul;128(2):619–627. doi: 10.1016/0008-8749(90)90053-t. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. Ullrich R., Zeitz M., Riecken E. O. Enteric immunologic abnormalities in human immunodeficiency virus infection. Semin Liver Dis. 1992 May;12(2):167–174. doi: 10.1055/s-2007-1007388. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Zeitz M., Quinn T. C., Graeff A. S., James S. P. Mucosal T cells provide helper function but do not proliferate when stimulated by specific antigen in lymphogranuloma venereum proctitis in nonhuman primates. Gastroenterology. 1988 Feb;94(2):353–366. doi: 10.1016/0016-5085(88)90422-2. [DOI] [PubMed] [Google Scholar]
  26. 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]

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