Abstract
MoAbs and immunoperoxidase methods were used to identify antigen-presenting and phagocytic cells and to assess expression of HLA-DR molecules on cells obtained by bronchoalveolar lavage (BAL) from 33 AIDS patients and nine normal volunteers. In 17 patients, not receiving antiretroviral therapy, the expression of HLA-DR molecules (MoAb RFDR1) as well as the percentages of cells expressing RFD1 marker for antigen-presenting cells and RFD7 marker for mature phagocytes were significantly reduced. However, in BAL obtained after commencing treatment with zidovudine (AZT) in 21 patients or with 2',3'-dideoxyinosine (DDI) in five patients, the expression of the markers studied was found to have returned to levels of expression seen in normal lavages. The changes observed were clearly associated with antiretroviral treatment and did not correlate with applications of other drugs, blood CD4 counts or presence of infectious organisms in BAL fluid. As the alterations in the expression of HLA-DR molecules and RFD1 marker on macrophages have been shown to be associated with functional capacities of these cells, the reversal of impaired expression of phenotypic markers on alveolar macrophages in AIDS patients by AZT and DDI signifies an important ability of these drugs to modify immune reactivity and emphasizes the need to monitor such functions in HIV disease.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Belsito D. V., Sanchez M. R., Baer R. L., Valentine F., Thorbecke G. J. Reduced Langerhans' cell Ia antigen and ATPase activity in patients with the acquired immunodeficiency syndrome. N Engl J Med. 1984 May 17;310(20):1279–1282. doi: 10.1056/NEJM198405173102002. [DOI] [PubMed] [Google Scholar]
- Bray D. H., Squire S. B., Bagdades E., Mulvenna P. M., Johnson M. A., Poulter L. W. Alveolar macrophage populations are distorted in immunocompromised patients with pneumonitis. Eur Respir J. 1992 May;5(5):545–552. [PubMed] [Google Scholar]
- Campbell D. A., Poulter L. W., du Bois R. M. Immunocompetent cells in bronchoalveolar lavage reflect the cell populations in transbronchial biopsies in pulmonary sarcoidosis. Am Rev Respir Dis. 1985 Dec;132(6):1300–1306. doi: 10.1164/arrd.1985.132.6.1300. [DOI] [PubMed] [Google Scholar]
- Chayt K. J., Harper M. E., Marselle L. M., Lewin E. B., Rose R. M., Oleske J. M., Epstein L. G., Wong-Staal F., Gallo R. C. Detection of HTLV-III RNA in lungs of patients with AIDS and pulmonary involvement. JAMA. 1986 Nov 7;256(17):2356–2359. [PubMed] [Google Scholar]
- Fischl M. A., Richman D. D., Grieco M. H., Gottlieb M. S., Volberding P. A., Laskin O. L., Leedom J. M., Groopman J. E., Mildvan D., Schooley R. T. The efficacy of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial. N Engl J Med. 1987 Jul 23;317(4):185–191. doi: 10.1056/NEJM198707233170401. [DOI] [PubMed] [Google Scholar]
- 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]
- Griffiths P. D., Panjwani D. D., Stirk P. R., Ball M. G., Ganczakowski M., Blacklock H. A., Prentice H. G. Rapid diagnosis of cytomegalovirus infection in immunocompromised patients by detection of early antigen fluorescent foci. Lancet. 1984 Dec 1;2(8414):1242–1245. doi: 10.1016/s0140-6736(84)92797-1. [DOI] [PubMed] [Google Scholar]
- Heagy W., Kelley V. E., Strom T. B., Mayer K., Shapiro H. M., Mandel R., Finberg R. Decreased expression of human class II antigens on monocytes from patients with acquired immune deficiency syndrome. Increased expression with interferon-gamma. J Clin Invest. 1984 Dec;74(6):2089–2096. doi: 10.1172/JCI111633. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Janossy G., Bofill M., Poulter L. W., Rawlings E., Burford G. D., Navarrete C., Ziegler A., Kelemen E. Separate ontogeny of two macrophage-like accessory cell populations in the human fetus. J Immunol. 1986 Jun 15;136(12):4354–4361. [PubMed] [Google Scholar]
- Linette G. P., Hartzman R. J., Ledbetter J. A., June C. H. HIV-1-infected T cells show a selective signaling defect after perturbation of CD3/antigen receptor. Science. 1988 Jul 29;241(4865):573–576. doi: 10.1126/science.2899908. [DOI] [PubMed] [Google Scholar]
- Macatonia S. E., Lau R., Patterson S., Pinching A. J., Knight S. C. Dendritic cell infection, depletion and dysfunction in HIV-infected individuals. Immunology. 1990 Sep;71(1):38–45. [PMC free article] [PubMed] [Google Scholar]
- Meltzer M. S., Skillman D. R., Gomatos P. J., Kalter D. C., Gendelman H. E. Role of mononuclear phagocytes in the pathogenesis of human immunodeficiency virus infection. Annu Rev Immunol. 1990;8:169–194. doi: 10.1146/annurev.iy.08.040190.001125. [DOI] [PubMed] [Google Scholar]
- Noble B., Du Bois R. M., Poulter L. W. The distribution of phenotypically distinct macrophage subsets in the lungs of patients with cryptogenic fibrosing alveolitis. Clin Exp Immunol. 1989 Apr;76(1):41–46. [PMC free article] [PubMed] [Google Scholar]
- Ohtsuka M., Yoshizawa Y., Sato T., Yano H., Mukai R., Hasegawa S., Moore V. L. Accessory cell function of human alveolar macrophages in antigen-induced T lymphocyte proliferation. Int Arch Allergy Appl Immunol. 1989;90(1):97–103. doi: 10.1159/000235007. [DOI] [PubMed] [Google Scholar]
- Petit A. J., Terpstra F. G., Miedema F. Human immunodeficiency virus infection down-regulates HLA class II expression and induces differentiation in promonocytic U937 cells. J Clin Invest. 1987 Jun;79(6):1883–1889. doi: 10.1172/JCI113032. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Poulter L. W., Campbell D. A., Munro C., Janossy G. Discrimination of human macrophages and dendritic cells by means of monoclonal antibodies. Scand J Immunol. 1986 Sep;24(3):351–357. doi: 10.1111/j.1365-3083.1986.tb02104.x. [DOI] [PubMed] [Google Scholar]
- Poulter L. W. Changes in lung macrophages during disease. FEMS Microbiol Immunol. 1990 Dec;2(5-6):327–331. doi: 10.1111/j.1574-6968.1990.tb03536.x. [DOI] [PubMed] [Google Scholar]
- Roy G., Rojo N., Leyva-Cobián F. Phenotypic changes in monocytes and alveolar macrophages in patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC). J Clin Lab Immunol. 1987 Jul;23(3):135–141. [PubMed] [Google Scholar]
- Simmonds P., Beatson D., Cuthbert R. J., Watson H., Reynolds B., Peutherer J. F., Parry J. V., Ludlam C. A., Steel C. M. Determinants of HIV disease progression: six-year longitudinal study in the Edinburgh haemophilia/HIV cohort. Lancet. 1991 Nov 9;338(8776):1159–1163. doi: 10.1016/0140-6736(91)92029-2. [DOI] [PubMed] [Google Scholar]
- Spiteri M. A., Newman S. P., Clarke S. W., Poulter L. W. Inhaled corticosteroids can modulate the immunopathogenesis of pulmonary sarcoidosis. Eur Respir J. 1989 Mar;2(3):218–224. [PubMed] [Google Scholar]
- Spiteri M. A., Poulter L. W. Characterization of immune inducer and suppressor macrophages from the normal human lung. Clin Exp Immunol. 1991 Jan;83(1):157–162. doi: 10.1111/j.1365-2249.1991.tb05607.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Squire S. B., Elford J., Bor R., Tilsed G., Salt H., Bagdades E. K., Janossy G., Griffiths P. D., Johnson M. A. Open access clinic providing HIV-I antibody results on day of testing: the first twelve months. BMJ. 1991 Jun 8;302(6789):1383–1386. doi: 10.1136/bmj.302.6789.1383. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Takemura R., Werb Z. Secretory products of macrophages and their physiological functions. Am J Physiol. 1984 Jan;246(1 Pt 1):C1–C9. doi: 10.1152/ajpcell.1984.246.1.C1. [DOI] [PubMed] [Google Scholar]
- Unanue E. R., Allen P. M. The basis for the immunoregulatory role of macrophages and other accessory cells. Science. 1987 May 1;236(4801):551–557. doi: 10.1126/science.2437650. [DOI] [PubMed] [Google Scholar]
- Ziza J. M., Brun-Vezinet F., Venet A., Rouzioux C. H., Traversat J., Israel-Biet B., Barre-Sinoussi F., Chermann J. C., Godeau P. Lymphadenopathy-associated virus isolated from bronchoalveolar lavage fluid in AIDS-related complex with lymphoid interstitial pneumonitis. N Engl J Med. 1985 Jul 18;313(3):183–183. doi: 10.1056/NEJM198507183130313. [DOI] [PubMed] [Google Scholar]