Abstract
We have investigated CD4+ T-cell autoreactivity to normal syngeneic B cells in vitro in chronic experimental Chagas' disease. Resting B cells induced an intense proliferative response and lymphokine secretion by splenic CD4+ T cells from Trypanosoma cruzi-infected (8 months or more of infection) donors, compared to much lower responses by uninfected controls. On the other hand, lipopolysaccharide-activated B cells induced syngeneic CD4+ T-cell activation in both control and infected groups. The observed syngeneic T-B-cell cooperation was bidirectional. In the absence of any exogenous stimulus, CD4+ T cells from T. cruzi-infected animals induced much higher production of all tested immunoglobulin (Ig) isotypes (IgM, IgG1, IgG2a, IgG2b, IgG3) by syngeneic B cells, compared to T cells from uninfected donors. When lipopolysaccharide-treated B cells were used, CD4+ T cells from either control or infected donors enhanced IgG1 and IgG3 production, but only CD4+ T cells of infected origin induced IgG2a production in this system without addition of exogenous gamma interferon. Enhanced T-cell proliferation and Ig production were also observed with highly purified CD4+ T cells and in serum-free medium. Both proliferation and Ig production could be blocked with anti-major histocompatibility complex class II monoclonal antibodies. Enhanced reactivity and help for Ig production were seen only in response to syngeneic BALB B cells and not in response to allogeneic B10 B cells. These results indicate that chronic infection with T. cruzi results in increased CD4+ T-cell reactivity towards syngeneic B cells, which leads to spontaneous Ig production. These autoreactive T cells might play a role in polyclonal autoantibody production in chronic Chagas' disease.
Full Text
The Full Text of this article is available as a PDF (313.7 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Contreras V. T., Salles J. M., Thomas N., Morel C. M., Goldenberg S. In vitro differentiation of Trypanosoma cruzi under chemically defined conditions. Mol Biochem Parasitol. 1985 Sep;16(3):315–327. doi: 10.1016/0166-6851(85)90073-8. [DOI] [PubMed] [Google Scholar]
- Cossio P. M., Diez C., Szarfman A., Kreutzer E., Candiolo B., Arana R. M. Chagasic cardiopathy. Demonstration of a serum gamma globulin factor which reacts with endocardium and vascular structures. Circulation. 1974 Jan;49(1):13–21. doi: 10.1161/01.cir.49.1.13. [DOI] [PubMed] [Google Scholar]
- D'Imperio Lima M. R., Joskowicz M., Coutinho A., Kipnis T., Eisen H. Very large and isotypically atypical polyclonal plaque-forming cell responses in mice infected with Trypanosoma cruzi. Eur J Immunol. 1985 Feb;15(2):201–203. doi: 10.1002/eji.1830150219. [DOI] [PubMed] [Google Scholar]
- DosReis G. A., Shevach E. M. Analysis of autoreactive I region-restricted T cell colonies isolated from the guinea pig syngeneic mixed leukocyte reaction and from immune responses to conventional foreign antigens. Eur J Immunol. 1985 May;15(5):466–472. doi: 10.1002/eji.1830150510. [DOI] [PubMed] [Google Scholar]
- Dutra W. O., Martins-Filho O. A., Cançado J. R., Pinto-Dias J. C., Brener Z., Freeman Júnior G. L., Colley D. G., Gazzinelli G., Parra J. C. Activated T and B lymphocytes in peripheral blood of patients with Chagas' disease. Int Immunol. 1994 Apr;6(4):499–506. doi: 10.1093/intimm/6.4.499. [DOI] [PubMed] [Google Scholar]
- Finnegan A., Needleman B. W., Hodes R. J. Function of autoreactive T cells in immune responses. Immunol Rev. 1990 Aug;116:15–31. doi: 10.1111/j.1600-065x.1990.tb00802.x. [DOI] [PubMed] [Google Scholar]
- Gazzinelli R. T., Morato M. J., Nunes R. M., Cançado J. R., Brener Z., Gazzinelli G. Idiotype stimulation of T lymphocytes from Trypanosoma cruzi-infected patients. J Immunol. 1988 May 1;140(9):3167–3172. [PubMed] [Google Scholar]
- Gazzinelli R. T. Natural anti-Gal antibodies prevent, rather than cause, autoimmunity in human Chagas' disease. Res Immunol. 1991 Feb;142(2):164–167. doi: 10.1016/0923-2494(91)90031-d. [DOI] [PubMed] [Google Scholar]
- Inaba K., Steinman R. M. Resting and sensitized T lymphocytes exhibit distinct stimulatory (antigen-presenting cell) requirements for growth and lymphokine release. J Exp Med. 1984 Dec 1;160(6):1717–1735. doi: 10.1084/jem.160.6.1717. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jones E. M., Colley D. G., Tostes S., Lopes E. R., Vnencak-Jones C. L., McCurley T. L. Amplification of a Trypanosoma cruzi DNA sequence from inflammatory lesions in human chagasic cardiomyopathy. Am J Trop Med Hyg. 1993 Mar;48(3):348–357. doi: 10.4269/ajtmh.1993.48.348. [DOI] [PubMed] [Google Scholar]
- Krieger J. I., Chesnut R. W., Grey H. M. Capacity of B cells to function as stimulators of a primary mixed leukocyte reaction. J Immunol. 1986 Nov 15;137(10):3117–3123. [PubMed] [Google Scholar]
- Laguens R. P., Meckert P. C., Chambo G., Gelpi R. J. Chronic Chagas disease in the mouse. II. Transfer of the heart disease by means of immunocompetent cells. Medicina (B Aires) 1981;41(1):40–43. [PubMed] [Google Scholar]
- Laguens R. P., Meckert P. C., Chambó J. G. Antiheart antibody-dependent cytotoxicity in the sera of mice chronically infected with Trypanosoma cruzi. Infect Immun. 1988 Apr;56(4):993–997. doi: 10.1128/iai.56.4.993-997.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Levitus G., Hontebeyrie-Joskowicz M., Van Regenmortel M. H., Levin M. J. Humoral autoimmune response to ribosomal P proteins in chronic Chagas heart disease. Clin Exp Immunol. 1991 Sep;85(3):413–417. doi: 10.1111/j.1365-2249.1991.tb05741.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lopes M. F., Cunha J. M., Bezerra F. L., Gonzalez M. S., Gomes J. E., Lapa e Silva J. R., Garcia E. S., Dos Reis G. A. Trypanosoma cruzi: both chemically induced and triatomine-derived metacyclic trypomastigotes cause the same immunological disturbances in the infected mammalian host. Exp Parasitol. 1995 Mar;80(2):194–204. doi: 10.1006/expr.1995.1024. [DOI] [PubMed] [Google Scholar]
- Lopes M. F., da Veiga V. F., Santos A. R., Fonseca M. E., DosReis G. A. Activation-induced CD4+ T cell death by apoptosis in experimental Chagas' disease. J Immunol. 1995 Jan 15;154(2):744–752. [PubMed] [Google Scholar]
- Minoprio P., Eisen H., Joskowicz M., Pereira P., Coutinho A. Suppression of polyclonal antibody production in Trypanosoma cruzi-infected mice by treatment with anti-L3T4 antibodies. J Immunol. 1987 Jul 15;139(2):545–550. [PubMed] [Google Scholar]
- Molina H. A., Milei J., Storino R. Chronic Chagas' myocardiopathy. Demonstration of in vivo bound immunoglobulins in heart structures by the immunoperoxidase technique. Cardiology. 1984;71(6):297–306. doi: 10.1159/000173683. [DOI] [PubMed] [Google Scholar]
- Nobrega A., Haury M., Grandien A., Malanchère E., Sundblad A., Coutinho A. Global analysis of antibody repertoires. II. Evidence for specificity, self-selection and the immunological "homunculus" of antibodies in normal serum. Eur J Immunol. 1993 Nov;23(11):2851–2859. doi: 10.1002/eji.1830231119. [DOI] [PubMed] [Google Scholar]
- Ortiz-Ortiz L., Parks D. E., Rodriguez M., Weigle W. O. Polyclonal B lymphocyte activation during Trypanosoma cruzi infection. J Immunol. 1980 Jan;124(1):121–126. [PubMed] [Google Scholar]
- Petry K., Eisen H. Chagas disease: a model for the study of autoimmune diseases. Parasitol Today. 1989 Apr;5(4):111–116. doi: 10.1016/0169-4758(89)90052-5. [DOI] [PubMed] [Google Scholar]
- Russo M., Starobinas N., Minoprio P., Coutinho A., Hontebeyrie-Joskowicz M. Parasitic load increases and myocardial inflammation decreases in Trypanosoma cruzi-infected mice after inactivation of helper T cells. Ann Inst Pasteur Immunol. 1988 May-Jun;139(3):225–236. doi: 10.1016/0769-2625(88)90136-5. [DOI] [PubMed] [Google Scholar]
- Snapper C. M., Peschel C., Paul W. E. IFN-gamma stimulates IgG2a secretion by murine B cells stimulated with bacterial lipopolysaccharide. J Immunol. 1988 Apr 1;140(7):2121–2127. [PubMed] [Google Scholar]
- Spinella S., Liegeard P., Hontebeyrie-Joskowicz M. Trypanosoma cruzi: predominance of IgG2a in nonspecific humoral response during experimental Chagas' disease. Exp Parasitol. 1992 Feb;74(1):46–56. doi: 10.1016/0014-4894(92)90138-z. [DOI] [PubMed] [Google Scholar]
- Spinella S., Milon G., Hontebeyrie-Joskowicz M. A CD4+ TH2 cell line isolated from mice chronically infected with Trypanosoma cruzi induces IgG2 polyclonal response in vivo. Eur J Immunol. 1990 May;20(5):1045–1051. doi: 10.1002/eji.1830200515. [DOI] [PubMed] [Google Scholar]
- Szarfman A., Terranova V. P., Rennard S. I., Foidart J. M., de Fatima Lima M., Scheinman J. I., Martin G. R. Antibodies to laminin in Chagas' disease. J Exp Med. 1982 Apr 1;155(4):1161–1171. doi: 10.1084/jem.155.4.1161. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tilkin A. F., Michon J., Juy D., Kayibanda M., Henin Y., Sterkers G., Betuel H., Lévy J. P. Autoreactive T cell clones of MHC class II specificities are produced during responses against foreign antigens in man. J Immunol. 1987 Feb 1;138(3):674–679. [PubMed] [Google Scholar]
- Van Voorhis W. C., Eisen H. Fl-160. A surface antigen of Trypanosoma cruzi that mimics mammalian nervous tissue. J Exp Med. 1989 Mar 1;169(3):641–652. doi: 10.1084/jem.169.3.641. [DOI] [PMC free article] [PubMed] [Google Scholar]
- d'Imperio Lima M. R., Eisen H., Minoprio P., Joskowicz M., Coutinho A. Persistence of polyclonal B cell activation with undetectable parasitemia in late stages of experimental Chagas' disease. J Immunol. 1986 Jul 1;137(1):353–356. [PubMed] [Google Scholar]