Abstract
To help define the immunoregulatory defects in patients with onchocerciasis, flow cytometric analysis of circulating lymphocyte subpopulations was performed in parallel with functional assays. No significant differences in CD4/CD8 ratios were seen when microfilariae-positive individuals from Guatemala were compared with Guatemalan controls. However, the infected individuals had significantly increased numbers of circulating CD4+CD45RA+ lymphocytes (mean 38.3%) when compared with controls (mean 16.0%). Coexpression of the activation marker HLA-DR was significantly increased on CD4+ cells from infected individuals. In contrast, no up-regulation of HLA-DR was seen on CD8+ or CD19+ cells. At 1 year after initiation of treatment with semiannual doses of the microfilaricide ivermectin, there were significant increases (P less than 0.05) in the percentage of CD4+CD45RA- cells, the percentage of CD4+HLA-DR+ cells, and mitogen-induced lymphokine production (IL-2, IL-4). Despite these changes, parasite-specific IL-2 and IL-4 production which had been undetectable before treatment did not manifest itself even by the 2-yr follow-up. Defects in the T-cell activation pathway in Onchocerca volvulus-infected individuals may thus exist at several independent points; a state of parasite antigen-specific tolerance appears to remain even after the relative reversal of other generalized immunoregulatory defects.
Full text
PDF







Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Akbar A. N., Terry L., Timms A., Beverley P. C., Janossy G. Loss of CD45R and gain of UCHL1 reactivity is a feature of primed T cells. J Immunol. 1988 Apr 1;140(7):2171–2178. [PubMed] [Google Scholar]
- Bartlett A., Turk J., Ngu J., Mackenzie C. D., Fuglsang H. Variation in delayed hypersensitivity in onchocerciasis. Trans R Soc Trop Med Hyg. 1978;72(4):372–377. doi: 10.1016/0035-9203(78)90130-x. [DOI] [PubMed] [Google Scholar]
- Brattig N. W., Tischendorf F. W., Albiez E. J., Büttner D. W., Berger J. Distribution pattern of peripheral lymphocyte subsets in localized and generalized form of onchocerciasis. Clin Immunol Immunopathol. 1987 Aug;44(2):149–159. doi: 10.1016/0090-1229(87)90062-6. [DOI] [PubMed] [Google Scholar]
- Buck A. A., Anderson R. I., Colston J. A., Jr, Wallace C. K., Connor D. H., Harman L. E., Jr, Donner M. W., Ganley J. P. Microfilaruria in onchocerciasis. A clinical and epidemiological follow-up study in the Republic of Chad. Bull World Health Organ. 1971;45(3):353–369. [PMC free article] [PubMed] [Google Scholar]
- Chrétien I., Van Kimmenade A., Pearce M. K., Banchereau J., Abrams J. S. Development of polyclonal and monoclonal antibodies for immunoassay and neutralization of human interleukin-4. J Immunol Methods. 1989 Feb 8;117(1):67–81. doi: 10.1016/0022-1759(89)90120-8. [DOI] [PubMed] [Google Scholar]
- Cillari E., Milano S., Dieli M., Maltese E., Di Rosa S., Mansueto S., Salerno A., Liew F. Y. Reduction in the number of UCHL-1+ cells and IL-2 production in the peripheral blood of patients with visceral leishmaniasis. J Immunol. 1991 Feb 1;146(3):1026–1030. [PubMed] [Google Scholar]
- Emery P., Gentry K. C., Mackay I. R., Muirden K. D., Rowley M. Deficiency of the suppressor inducer subset of T lymphocytes in rheumatoid arthritis. Arthritis Rheum. 1987 Aug;30(8):849–856. doi: 10.1002/art.1780300802. [DOI] [PubMed] [Google Scholar]
- Gallin M., Edmonds K., Ellner J. J., Erttmann K. D., White A. T., Newland H. S., Taylor H. R., Greene B. M. Cell-mediated immune responses in human infection with Onchocerca volvulus. J Immunol. 1988 Mar 15;140(6):1999–2007. [PubMed] [Google Scholar]
- Greene B. M., Fanning M. M., Ellner J. J. Non-specific suppression of antigen-induced lymphocyte blastogenesis in Onchocerca volvulus infection in man. Clin Exp Immunol. 1983 May;52(2):259–265. [PMC free article] [PubMed] [Google Scholar]
- Greene B. M., Gbakima A. A., Albiez E. J., Taylor H. R. Humoral and cellular immune responses to Onchocerca volvulus infection in humans. Rev Infect Dis. 1985 Nov-Dec;7(6):789–795. doi: 10.1093/clinids/7.6.789. [DOI] [PubMed] [Google Scholar]
- Kilian H. D., Nielsen G. Cell-mediated and humoral immune response to tetanus vaccinations in onchocerciasis patients. Trop Med Parasitol. 1989 Sep;40(3):285–291. [PubMed] [Google Scholar]
- Lal R. B., Edison L. J., Chused T. M. Fixation and long-term storage of human lymphocytes for surface marker analysis by flow cytometry. Cytometry. 1988 May;9(3):213–219. doi: 10.1002/cyto.990090305. [DOI] [PubMed] [Google Scholar]
- Lal R. B., Kumaraswami V., Krishnan N., Nutman T. B., Ottesen E. A. Lymphocyte subpopulations in Bancroftian filariasis: activated (DR+) CD8+ T cells in patients with chronic lymphatic obstruction. Clin Exp Immunol. 1989 Jul;77(1):77–82. [PMC free article] [PubMed] [Google Scholar]
- Lammie P. J., Eberhard M. L., Leiva L. E., Lowrie R. C., Jr, Katz S. P. The effect of diethylcarbamazine treatment of Bancroftian filariasis on the immunological reactivity of microfilaraemic individuals. Trans R Soc Trop Med Hyg. 1988;82(5):726–729. doi: 10.1016/0035-9203(88)90216-7. [DOI] [PubMed] [Google Scholar]
- Lewis D. B., Prickett K. S., Larsen A., Grabstein K., Weaver M., Wilson C. B. Restricted production of interleukin 4 by activated human T cells. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9743–9747. doi: 10.1073/pnas.85.24.9743. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mackenzie C. D., Williams J. F., Sisley B. M., Steward M. W., O'Day J. Variations in host responses and the pathogenesis of human onchocerciasis. Rev Infect Dis. 1985 Nov-Dec;7(6):802–808. doi: 10.1093/clinids/7.6.802. [DOI] [PubMed] [Google Scholar]
- Modlin R. L., Melancon-Kaplan J., Young S. M., Pirmez C., Kino H., Convit J., Rea T. H., Bloom B. R. Learning from lesions: patterns of tissue inflammation in leprosy. Proc Natl Acad Sci U S A. 1988 Feb;85(4):1213–1217. doi: 10.1073/pnas.85.4.1213. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Morimoto C., Hafler D. A., Weiner H. L., Letvin N. L., Hagan M., Daley J., Schlossman S. F. Selective loss of the suppressor-inducer T-cell subset in progressive multiple sclerosis. Analysis with anti-2H4 monoclonal antibody. N Engl J Med. 1987 Jan 8;316(2):67–72. doi: 10.1056/NEJM198701083160202. [DOI] [PubMed] [Google Scholar]
- Morimoto C., Letvin N. L., Distaso J. A., Aldrich W. R., Schlossman S. F. The isolation and characterization of the human suppressor inducer T cell subset. J Immunol. 1985 Mar;134(3):1508–1515. [PubMed] [Google Scholar]
- Morimoto C., Romain P. L., Fox D. A., Anderson P., DiMaggio M., Levine H., Schlossman S. F. Abnormalities in CD4+ T-lymphocyte subsets in inflammatory rheumatic diseases. Am J Med. 1988 May;84(5):817–825. doi: 10.1016/0002-9343(88)90058-7. [DOI] [PubMed] [Google Scholar]
- Mylvaganam R., Ahn Y. S., Sprinz P. G., Garcia R. O., Harrington W. J. Sex difference in the CD4 + CD45R+ T lymphocytes in normal individuals and its selective decrease in women with idiopathic thrombocytopenic purpura. Clin Immunol Immunopathol. 1989 Sep;52(3):473–485. doi: 10.1016/0090-1229(89)90161-x. [DOI] [PubMed] [Google Scholar]
- Ngu J. L. Immunological studies on onchocerciasis. Varying skin hypersensitivity and leucocyte migration inhibition in a clinical spectrum of the disease. Acta Trop. 1978 Sep;35(3):269–279. [PubMed] [Google Scholar]
- Nutman T. B., Kumaraswami V., Ottesen E. A. Parasite-specific anergy in human filariasis. Insights after analysis of parasite antigen-driven lymphokine production. J Clin Invest. 1987 May;79(5):1516–1523. doi: 10.1172/JCI112982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ouaissi M. A., Dessaint J. P., Cornette J., Desmoutis I., Capron A. Induction of non-specific human suppressor cells in vitro by defined Onchocerca volvulus antigens. Clin Exp Immunol. 1983 Sep;53(3):634–644. [PMC free article] [PubMed] [Google Scholar]
- Piessens W. F., Ratiwayanto S., Piessens P. W., Tuti S., McGreevy P. B., Darwis F., Palmieri J. R., Koiman I., Dennis D. T. Effect of treatment with diethylcarbamazine on immune responses to filarial antigens in patients infected with Brugia malayi. Acta Trop. 1981 Sep;38(3):227–234. [PubMed] [Google Scholar]
- Prost A., Nebout M., Rougemont A. Lepromatous leprosy and onchocerciasis. Br Med J. 1979 Mar 3;1(6163):589–590. doi: 10.1136/bmj.1.6163.589-a. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rougemont A., Boisson-Pontal M. E., Pontal P. G., Gridel F., Sangare S. Tuberculin skin tests and B.C.G. vaccination in hyperendemic area of onchocerciasis. Lancet. 1977 Feb 5;1(8006):309–309. doi: 10.1016/s0140-6736(77)91857-8. [DOI] [PubMed] [Google Scholar]
- Salmon M., Kitas G. D., Bacon P. A. Production of lymphokine mRNA by CD45R+ and CD45R- helper T cells from human peripheral blood and by human CD4+ T cell clones. J Immunol. 1989 Aug 1;143(3):907–912. [PubMed] [Google Scholar]
- Sanders M. E., Makgoba M. W., Shaw S. Human naive and memory T cells: reinterpretation of helper-inducer and suppressor-inducer subsets. Immunol Today. 1988 Jul-Aug;9(7-8):195–199. doi: 10.1016/0167-5699(88)91212-1. [DOI] [PubMed] [Google Scholar]
- Verwilghen J., Vertessen S., Stevens E. A., Dequeker J., Ceuppens J. L. Depressed T-cell reactivity to recall antigens in rheumatoid arthritis. J Clin Immunol. 1990 Mar;10(2):90–98. doi: 10.1007/BF00918190. [DOI] [PubMed] [Google Scholar]
- Ward D. J., Nutman T. B., Zea-Flores G., Portocarrero C., Lujan A., Ottesen E. A. Onchocerciasis and immunity in humans: enhanced T cell responsiveness to parasite antigen in putatively immune individuals. J Infect Dis. 1988 Mar;157(3):536–543. doi: 10.1093/infdis/157.3.536. [DOI] [PubMed] [Google Scholar]
- Yachie A., Miyawaki T., Uwadana N., Ohzeki S., Taniguchi N. Sequential expression of T cell activation (Tac) antigen and Ia determinants on circulating human T cells after immunization with tetanus toxoid. J Immunol. 1983 Aug;131(2):731–735. [PubMed] [Google Scholar]
- 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]
- Zwingenberger K., Harms G., Pedrosa C., Omena S., Sandkamp B., Neifer S. Determinants of the immune response in visceral leishmaniasis: evidence for predominance of endogenous interleukin 4 over interferon-gamma production. Clin Immunol Immunopathol. 1990 Nov;57(2):242–249. doi: 10.1016/0090-1229(90)90038-r. [DOI] [PubMed] [Google Scholar]
- al-Kassab A. S., Raziuddin S. Immune activation and T cell subset abnormalities in circulation of patients with recently diagnosed type I diabetes mellitus. Clin Exp Immunol. 1990 Aug;81(2):267–271. doi: 10.1111/j.1365-2249.1990.tb03329.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
