Abstract
To explore the mechanisms of antigen-specific immune unresponsiveness seen in microfilaremic patients with bancroftian filariasis, T and B cell precursor frequency analysis was performed using PBMC from individuals with either asymptomatic microfilaremia (MF, n = 7) or chronic lymphatic obstruction (CP, n = 20). Highly purified CD3+ cells were partially reconstituted with adherent cells and their proliferative response to parasite antigens determined in cultures of T cells by limiting dilution analysis. A filter immunoplaque assay also assessed the frequency of both total and parasite-specific Ig-producing B cells. While the lymphocyte proliferation to mitogens and to a nonparasite antigen (Streptolysin-O, [SLO]) were similar in all groups of patients, the frequency of parasite-specific CD3+ T cells was significantly lower (geometric mean [GM], 1/3,757) in MF patients when compared to that in CP patients (GM 1/1,513; P less than 0.001). Similarly, the proportion of lymphocytes producing parasite-specific IgE or IgG was significantly lower in MF patients (IgE mean, 0.2%; IgG mean, 0.33%) compared with CP patients (IgE mean, 3.2%; IgG mean, 1.76%; P less than 0.05 for both comparisons). These observations imply that low numbers of parasite-specific T and B lymphocytes may be partially responsible for the severely diminished capacity of lymphocytes from patients with MF to produce parasite-specific antibody and to proliferate to parasite antigen in vitro. Such differences in parasite-specific lymphocyte responses suggest that tolerance by clonal anergy may be a critical mechanism for maintaining the microfilaremic state.
Full text
PDF







Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Alling D. W. Estimation of hit number. Biometrics. 1971 Sep;27(3):605–613. [PubMed] [Google Scholar]
- Brett S. J., Kingston A. E., Colston M. J. Limiting dilution analysis of the human T cell response to mycobacterial antigens from BCG vaccinated individuals and leprosy patients. Clin Exp Immunol. 1987 Jun;68(3):510–520. [PMC free article] [PubMed] [Google Scholar]
- Carvalho E. M., Bacellar O., Barral A., Badaro R., Johnson W. D., Jr Antigen-specific immunosuppression in visceral leishmaniasis is cell mediated. J Clin Invest. 1989 Mar;83(3):860–864. doi: 10.1172/JCI113969. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Del Prete G. F., De Carli M., Mastromauro C., Biagiotti R., Macchia D., Falagiani P., Ricci M., Romagnani S. Purified protein derivative of Mycobacterium tuberculosis and excretory-secretory antigen(s) of Toxocara canis expand in vitro human T cells with stable and opposite (type 1 T helper or type 2 T helper) profile of cytokine production. J Clin Invest. 1991 Jul;88(1):346–350. doi: 10.1172/JCI115300. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fey K., Melchers I., Eichmann K. Quantitative studies on T cell diversity. IV. Mathematical analysis of multiple limiting populations of effector and suppressor T cells. J Exp Med. 1983 Jul 1;158(1):40–52. doi: 10.1084/jem.158.1.40. [DOI] [PMC free article] [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]
- Hussain R., Hamilton R. G., Kumaraswami V., Adkinson N. F., Jr, Ottesen E. A. IgE responses in human filariasis. I. Quantitation of filaria-specific IgE. J Immunol. 1981 Oct;127(4):1623–1629. [PubMed] [Google Scholar]
- Kaplan G., Gandhi R. R., Weinstein D. E., Levis W. R., Patarroyo M. E., Brennan P. J., Cohn Z. A. Mycobacterium leprae antigen-induced suppression of T cell proliferation in vitro. J Immunol. 1987 May 1;138(9):3028–3034. [PubMed] [Google Scholar]
- Kaplan G., Weinstein D. E., Steinman R. M., Levis W. R., Elvers U., Patarroyo M. E., Cohn Z. A. An analysis of in vitro T cell responsiveness in lepromatous leprosy. J Exp Med. 1985 Sep 1;162(3):917–929. doi: 10.1084/jem.162.3.917. [DOI] [PMC free article] [PubMed] [Google Scholar]
- King C. L., Poindexter R. W., Ragunathan J., Fleisher T. A., Ottesen E. A., Nutman T. B. Frequency analysis of IgE-secreting B lymphocytes in persons with normal or elevated serum IgE levels. J Immunol. 1991 Mar 1;146(5):1478–1483. [PubMed] [Google Scholar]
- Macy E., Kemeny M., Saxon A. Enhanced ELISA: how to measure less than 10 picograms of a specific protein (immunoglobulin) in less than 8 hours. FASEB J. 1988 Nov;2(14):3003–3009. doi: 10.1096/fasebj.2.14.3263291. [DOI] [PubMed] [Google Scholar]
- Matzinger P., Guerder S. Does T-cell tolerance require a dedicated antigen-presenting cell? Nature. 1989 Mar 2;338(6210):74–76. doi: 10.1038/338074a0. [DOI] [PubMed] [Google Scholar]
- McGreevy P. B., Ratiwayanto S., Tuti S., McGreevy M. M., Dennis D. T. Brugia malayi: relationship between anti-sheath antibodies and amicrofilaremia in natives living in an endemic area of South Kalimantan, Borneo. Am J Trop Med Hyg. 1980 Jul;29(4):553–562. doi: 10.4269/ajtmh.1980.29.553. [DOI] [PubMed] [Google Scholar]
- Melchers I., Fey K., Eichmann K. Quantitative studies on T cell diversity. III. Limiting dilution analysis of precursor cells for T helper cells reactive to xenogeneic erythrocytes. J Exp Med. 1982 Dec 1;156(6):1587–1603. doi: 10.1084/jem.156.6.1587. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mogensen C. E. The glomerular permeability determined by dextran clearance using Sephadex gel filtration. Scand J Clin Lab Invest. 1968;21(1):77–82. doi: 10.3109/00365516809076979. [DOI] [PubMed] [Google Scholar]
- 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]
- Nossal G. J. Immunologic tolerance: collaboration between antigen and lymphokines. Science. 1989 Jul 14;245(4914):147–153. doi: 10.1126/science.2526369. [DOI] [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]
- Nutman T. B., Kumaraswami V., Pao L., Narayanan P. R., Ottesen E. A. An analysis of in vitro B cell immune responsiveness in human lymphatic filariasis. J Immunol. 1987 Jun 1;138(11):3954–3959. [PubMed] [Google Scholar]
- Ojo-Amaize E. A., Salimonu L. S., Williams A. I., Akinwolere O. A., Shabo R., Alm G. V., Wigzell H. Positive correlation between degree of parasitemia, interferon titers, and natural killer cell activity in Plasmodium falciparum-infected children. J Immunol. 1981 Dec;127(6):2296–2300. [PubMed] [Google Scholar]
- Ottesen E. A. Modulation of the host response in human schistosomiasis. I. Adherent suppressor cells that inhibit lymphocyte proliferative responses to parasite antigens. J Immunol. 1979 Oct;123(4):1639–1644. [PubMed] [Google Scholar]
- Ottesen E. A., Weller P. F., Heck L. Specific cellular immune unresponsiveness in human filariasis. Immunology. 1977 Sep;33(3):413–421. [PMC free article] [PubMed] [Google Scholar]
- Ottesen E. A., Weller P. F., Lunde M. N., Hussain R. Endemic filariasis on a Pacific Island. II. Immunologic aspects: immunoglobulin, complement, and specific antifilarial IgG, IgM, and IgE antibodies. Am J Trop Med Hyg. 1982 Sep;31(5):953–961. [PubMed] [Google Scholar]
- Partono F., Oemijati S., Hudojo, Joesoef A., Sajidiman H., Putrali J., Clarke M. D., Carney W. P., Cross J. H. Malayan filariasis in Central Sulawesi (Celebes), Indonesia. Southeast Asian J Trop Med Public Health. 1977 Dec;8(4):452–458. [PubMed] [Google Scholar]
- Piessens W. F., McGreevy P. B., Piessens P. W., McGreevy M., Koiman I., Saroso J. S., Dennis D. T. Immune responses in human infections with Brugia malayi: specific cellular unresponsiveness to filarial antigens. J Clin Invest. 1980 Jan;65(1):172–179. doi: 10.1172/JCI109648. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Piessens W. F., McGreevy P. B., Piessens P. W., McGreevy M., Koiman I., Saroso J. S., Dennis D. T. Immune responses in human infections with Brugia malayi: specific cellular unresponsiveness to filarial antigens. J Clin Invest. 1980 Jan;65(1):172–179. doi: 10.1172/JCI109648. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Piessens W. F., Partono F., Hoffman S. L., Ratiwayanto S., Piessens P. W., Palmieri J. R., Koiman I., Dennis D. T., Carney W. P. Antigen-specific suppressor T lymphocytes in human lymphatic filariasis. N Engl J Med. 1982 Jul 15;307(3):144–148. doi: 10.1056/NEJM198207153070302. [DOI] [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]
- Piessens W. F., Ratiwayanto S., Tuti S., Palmieri J. H., Piessens P. W., Koiman I., Dennis D. T. Antigen-specific suppressor cells and suppressor factors in human filariasis with Brugia malayi. N Engl J Med. 1980 Apr 10;302(15):833–837. doi: 10.1056/NEJM198004103021503. [DOI] [PubMed] [Google Scholar]
- Sanjeevi C. B., Narayanan P. R. Antifilarial and anti PPD IgM antibodies in cord blood. Indian J Pediatr. 1989 Mar-Apr;56(2):207–211. doi: 10.1007/BF02726609. [DOI] [PubMed] [Google Scholar]
- Smedman L., Troye-Blomberg M., Perlmann H., Naucler A., Perlmann P. Phenotypic characterization of mononuclear white cells using finger-prick blood and light microscopy. Am J Trop Med Hyg. 1989 Jul;41(1):116–121. [PubMed] [Google Scholar]
- Taswell C. Limiting dilution assays for the determination of immunocompetent cell frequencies. I. Data analysis. J Immunol. 1981 Apr;126(4):1614–1619. [PubMed] [Google Scholar]
- Weil G. J., Hussain R., Kumaraswami V., Tripathy S. P., Phillips K. S., Ottesen E. A. Prenatal allergic sensitization to helminth antigens in offspring of parasite-infected mothers. J Clin Invest. 1983 May;71(5):1124–1129. doi: 10.1172/JCI110862. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weller P. F., Ottesen E. A. Failure of diethylcarbamazine as a provocative test in subperiodic Wuchereria bancrofti filariasis. Trans R Soc Trop Med Hyg. 1978;72(1):31–32. doi: 10.1016/0035-9203(78)90293-6. [DOI] [PubMed] [Google Scholar]
- Weller P. F., Ottesen E. A., Heck L. Immediate and delayed hypersensitivity skin test responses to the Dirofilaria immitis filarial skin test (Sawada) antigen in Wuchereria bancrofti filariasis. Am J Trop Med Hyg. 1980 Sep;29(5):809–814. doi: 10.4269/ajtmh.1980.29.809. [DOI] [PubMed] [Google Scholar]