Suppression of humoral immunity and lymphocyte responsiveness during experimental trypanosoma cruzi infections

O'daly, José A.; Simonis, Simonetta; Rolo, Nelva De; Caballero, Henry

doi:10.1590/S0036-46651984000200001

Abstracts

C3H/He and C57B1/6 mice were inoculated with 500 Trypanosoma cruzi trypomastigotes (Strain Y). During the acute phase infected mice presented parasitemia and enlargement of lymph nodes and spleens and intracellular parasites were observed in the heart. Examinations of cells derived from spleen and lymph nodes showed increased numbers of IgM and IgG-bearing cells. During the peak of splenomegaly, about day 17 post-infections, splenic lymphocytes showed a marked decrease in responsiveness to T and B-cell mitogens, parasite antigens and plaque forming cells (PFC) to sheep red blood cells (SRBC). Unfractionated or plastic adherent splenic cells from mice, obtained during the acute phase were able to suppress the response to mitogens by lymphocytes from uninfected mice. During the chronic phase. Disappearance of parasitemia and intracellular parasites in the hearts as well as a decrease in spleen size, was observed. These changes preceded the complete recovery of responsiveness to mitogens and T. cruzi antigens by C57B1/6 splenic lymphocytes. However, this recovery was only partial in the C3H/He mice, known to be more sensitive to T. cruzi infection. Partial recovery of humoral immune response also occurred in both strains of mice during the chronic phase.

Ratones C3H/He y C57B1/6 inoculados con 500 tripomastigotes de la cepa Y de T. cruzi muestran durante la fase aguda de la enferme-dad, parasitemia, aumento del bazo y gânglios linfáticos así como parásitos intracelulares en el corazón. Análisis de las células presentes en ganglios linfáticos y bazo presenta aumento de células IgM e IgG. Cuando la esplenomegalia es mayor, alrededor del día 17 postínfección, los linfocitos esplénicos mostraron un descenso marcado en la respuesta a mitógenos de células B y T, antígenos de T. cruzi y células formadoras de placas contra glóbulos rojos de carnero. Células de bazo o células esplénicas adherentes a plástico, obtenidas de ratones durante la fase aguda de la infección suprimen la respuesta a mitógenos de linfocitos normales. Durante la fase crónica, desaparece la parasitemia, los parásitos intracelulares en el corazón y disminuye la esplenomegalia. Estos cambios preceden a la recuperación de la respuesta a mitógenos y antígenos de T. cruzi en linfocitos esplénicos de C57B1/6. Esta recuperación es solo parcial en C3H/He, los cuales son más sen-sibles a la infección. También se encuentra recuperación de la respuesta humoral durante la fase crónica.

Suppression of humoral immunity and lymphocyte responsiveness during experimental trypanosoma cruzi infections

Supresión de la inmunidade humoral y de la respuesta linfocitaria durante la infección experimental con Trypanosoma cruzi

José A. O'daly; Simonetta Simonis; Nelva De Rolo; Henry Caballero

Center of Microbiology and Cell Biology. Instituto Venezolano de Investigaciones Científicas (I.V.I.C.). Apartado 1827, Caracas 1010 A, Venezuela

SUMMARY

C3H/He and C57B1/6 mice were inoculated with 500 Trypanosoma cruzi trypomastigotes (Strain Y). During the acute phase infected mice presented parasitemia and enlargement of lymph nodes and spleens and intracellular parasites were observed in the heart. Examinations of cells derived from spleen and lymph nodes showed increased numbers of IgM and IgG-bearing cells. During the peak of splenomegaly, about day 17 post-infections, splenic lymphocytes showed a marked decrease in responsiveness to T and B-cell mitogens, parasite antigens and plaque forming cells (PFC) to sheep red blood cells (SRBC). Unfractionated or plastic adherent splenic cells from mice, obtained during the acute phase were able to suppress the response to mitogens by lymphocytes from uninfected mice. During the chronic phase. Disappearance of parasitemia and intracellular parasites in the hearts as well as a decrease in spleen size, was observed. These changes preceded the complete recovery of responsiveness to mitogens and T. cruzi antigens by C57B1/6 splenic lymphocytes. However, this recovery was only partial in the C3H/He mice, known to be more sensitive to T. cruzi infection. Partial recovery of humoral immune response also occurred in both strains of mice during the chronic phase.

RESUMEN

Ratones C3H/He y C57B1/6 inoculados con 500 tripomastigotes de la cepa Y de T. cruzi muestran durante la fase aguda de la enferme-dad, parasitemia, aumento del bazo y gânglios linfáticos así como parásitos intracelulares en el corazón. Análisis de las células presentes en ganglios linfáticos y bazo presenta aumento de células IgM e IgG. Cuando la esplenomegalia es mayor, alrededor del día 17 postínfección, los linfocitos esplénicos mostraron un descenso marcado en la respuesta a mitógenos de células B y T, antígenos de T. cruzi y células formadoras de placas contra glóbulos rojos de carnero. Células de bazo o células esplénicas adherentes a plástico, obtenidas de ratones durante la fase aguda de la infección suprimen la respuesta a mitógenos de linfocitos normales. Durante la fase crónica, desaparece la parasitemia, los parásitos intracelulares en el corazón y disminuye la esplenomegalia. Estos cambios preceden a la recuperación de la respuesta a mitógenos y antígenos de T. cruzi en linfocitos esplénicos de C57B1/6. Esta recuperación es solo parcial en C3H/He, los cuales son más sen-sibles a la infección. También se encuentra recuperación de la respuesta humoral durante la fase crónica.

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ACKNOWLEDGMENTS

We thank Dr. Francisco Castillo and Dr. José Azocar for discussion and help in writing the manuscript and Miriam de León for excellent secretarial assistance.

2 CEBRA, J. J. & GOLDSTEIN, J. Chromatographic purification of tetramethylrhodamine-immunoglobulin conjugates and their use in the cellular localization of rabbit γglobulin polypeptide chains. J. Immunol. 95: 230-245, 1965.

Recebido para publicação em 10/1/1983.

1. ALBRIGHT, J. F.; DEITCHMAN, J. W.; HASSELL, S. A. & IZATO, K. Differential antibody production by adherent and nonadherent spleen cells transferred to irradiated and cyclophosphamide-treated recipient mice. J. Reticuloendothelial Soc. 17: 194-209, 1975.
3. CLINTON, B. A.; ORTIZ-ORTIZ, L.; GARCIA, W.; MARTINEZ, T. & CAPIN, R. Trypanosoma cruzi: early immune responses in infected mice. Exp. Parasitol. 37: 417-425, 1975.
4. CUNNINGHAM, D. S.; KUHN, R. E. & ROWLAND, E. C. Suppression of humoral responses during Trypanosoma cruzi infections in mice. Infect. Immun. 22: 155-160, 1978.
5. CUNNINGHAM, D. S. & KUHN, R. E. Trypanosoma cruzi: induced suppression substance. I. Cellular involvement and partial characterization. J. Immunol. 124: 2122-2199, 1980a.
6. CUNNINGHAM, D. S. & KUHN, R. E. Trypanosoma cruzi: induced suppression of the primary immune response in murine cell cultures to T-cell-dependent and independent antigens. J. Parasitol. 66: 16-27, 1980b.
7. CUNNINGHAM, D. S. & KUHN, R. E. Trypanosoma cruzi: induced suppressor substance. II. Regulatory activity. Immunogenetics 10: 557-571, 1980c.
8. ESURUOSO, G. O. The demonstration in vitro of the mitogenic effects of trypanosomal antigen on the spleen cells of normal, athymic and cyclophosphamide-treated mice. Clin. Exp. Immunol. 23: 314-317, 1976.
9. GOTTLIEB, D. F. Application of transformation to normalize the distribution of plaque forming cells. J. Immunol. 113: 51-57, 1974.
10. HAYES, M. M. & KIERSZENBAUM, F. Experimental Chagas' disease: Kinetics of lymphocyte responses and immunological control of the transition from acute to chronic Trypanosoma cruzi: infection. Infect. Immun. 31: 1117-1124, 1981.
11. JERNE, N. A.; HENRY, C; NORTH, A. A.; FUJI, H.; KOROS, A. C M. & LEFKOVITS, I. Plaque forming cells: Methodology and theory. Transplant. Rev. 18: 130-191, 1974.
12. KIERSZENBAUM, F. & PIENKOVSKY, L. Thymus dependent control of host defense mechanisms against Trypanosoma cruzi infection. Infect. Immun. 24: 117-120, 1979.
13. KIERSZENBAUM, F. & HAYES, M. M. Evaluation of lymphocyte responsiveness to polyclonal activators during acute and chronic experimental Trypanosoma cruzi: infection. Am. J. Trop. Med. Hyg. 29: 708-710, 1980.
14. LY, A. I. & MISHELL, R. I. Separation of mouse spleen cells by passage through columns of Sephadex G-10. J. Immunol. Meth. 5: 239-247, 1974.
15. O'DALY, J. A. A new liquid medium for Trypanosoma (Schizotrypanum) cruzi. Protozoology 22: 265-272, 1975.
16. O'DALY, J. A.; RODRIGUEZ, M. B.; GARLIN, G.; GIARDINA, S. & ZAIDENBERG, A. Growth requirements of T. cruzi at different temperatures Manuscript submitted for publication, 1982.
17. O'DALY, J. A.; SERRANO, L. E. & RODRIGUEZ, M. B. Free aminoacid pool and proteolytic enzymes in T. cruzi. Intern. J. Parasitology. In press.
18. RAMOS, C; SCHADTLER-SIWON, I. & ORTIZ-ORTIZ, L. Suppressor cells present in the spleens of Trypanosoma cruzi: infection mice. J. Immunol. 122: 1243-1247, 1979.
19. REED, L. J. & MUENCH, H. A simple method of estimating fifty per cent endpoints. Amer. J. Hyg. 27: 493-497, 1938.
20. REED, S. Adoptive transfer of resistance to acute Trypanosoma cruzi: infection with T-Iymphocyte-enriched spleen cells. Infect. Immun. 28: 404-410, 1980.
21. ROWLAND, E. C. & KUHN, R. E. Suppression of cellular responses in mice during Trypanosoma cruzi: infections. Infect. Immun. 20: 393-397, 1978.
22. SILVA, L. & NUSSENZWEIG, V. Sobre uma cepa de Trypanosoma cruzi: altamente virulenta para o ca-mundongo branco. Folia Clin. Biol. (São Paulo) 20: 191-208, 1953.
23. TEIXEIRA, A. R. L.; TEIXEIRA, G.; MACEDO, B. & PRATA, A. Acquired cell-mediated immunodepres-sion in acute Chagas'disease. J. Clin. Invest. 62: 1132-1141, 1978.
24. TRISCHMAN, T.; TANOWITZ, J.; WITTNER, M. & BLOOM, B. Trypanosoma cruzi: Role of the immune response in the natural resistance of inbred strains of mice. Exp. Parasitol 45: 160-168, 1978.

Publication Dates

Publication in this collection
12 Apr 2013
Date of issue
Apr 1984

History

Received
10 Jan 1983

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. ALBRIGHT, J. F.; DEITCHMAN, J. W.; HASSELL, S. A. & IZATO, K. Differential antibody production by adherent and nonadherent spleen cells transferred to irradiated and cyclophosphamide-treated recipient mice. J. Reticuloendothelial Soc. 17: 194-209, 1975.

[2] 3. CLINTON, B. A.; ORTIZ-ORTIZ, L.; GARCIA, W.; MARTINEZ, T. & CAPIN, R. Trypanosoma cruzi: early immune responses in infected mice. Exp. Parasitol. 37: 417-425, 1975.

[3] 4. CUNNINGHAM, D. S.; KUHN, R. E. & ROWLAND, E. C. Suppression of humoral responses during Trypanosoma cruzi infections in mice. Infect. Immun. 22: 155-160, 1978.

[4] 5. CUNNINGHAM, D. S. & KUHN, R. E. Trypanosoma cruzi: induced suppression substance. I. Cellular involvement and partial characterization. J. Immunol. 124: 2122-2199, 1980a.

[5] 6. CUNNINGHAM, D. S. & KUHN, R. E. Trypanosoma cruzi: induced suppression of the primary immune response in murine cell cultures to T-cell-dependent and independent antigens. J. Parasitol. 66: 16-27, 1980b.

[6] 7. CUNNINGHAM, D. S. & KUHN, R. E. Trypanosoma cruzi: induced suppressor substance. II. Regulatory activity. Immunogenetics 10: 557-571, 1980c.

[7] 8. ESURUOSO, G. O. The demonstration in vitro of the mitogenic effects of trypanosomal antigen on the spleen cells of normal, athymic and cyclophosphamide-treated mice. Clin. Exp. Immunol. 23: 314-317, 1976.

[8] 9. GOTTLIEB, D. F. Application of transformation to normalize the distribution of plaque forming cells. J. Immunol. 113: 51-57, 1974.

[9] 10. HAYES, M. M. & KIERSZENBAUM, F. Experimental Chagas' disease: Kinetics of lymphocyte responses and immunological control of the transition from acute to chronic Trypanosoma cruzi: infection. Infect. Immun. 31: 1117-1124, 1981.

[10] 11. JERNE, N. A.; HENRY, C; NORTH, A. A.; FUJI, H.; KOROS, A. C M. & LEFKOVITS, I. Plaque forming cells: Methodology and theory. Transplant. Rev. 18: 130-191, 1974.

[11] 12. KIERSZENBAUM, F. & PIENKOVSKY, L. Thymus dependent control of host defense mechanisms against Trypanosoma cruzi infection. Infect. Immun. 24: 117-120, 1979.

[12] 13. KIERSZENBAUM, F. & HAYES, M. M. Evaluation of lymphocyte responsiveness to polyclonal activators during acute and chronic experimental Trypanosoma cruzi: infection. Am. J. Trop. Med. Hyg. 29: 708-710, 1980.

[13] 14. LY, A. I. & MISHELL, R. I. Separation of mouse spleen cells by passage through columns of Sephadex G-10. J. Immunol. Meth. 5: 239-247, 1974.

[14] 15. O'DALY, J. A. A new liquid medium for Trypanosoma (Schizotrypanum) cruzi. Protozoology 22: 265-272, 1975.

[15] 16. O'DALY, J. A.; RODRIGUEZ, M. B.; GARLIN, G.; GIARDINA, S. & ZAIDENBERG, A. Growth requirements of T. cruzi at different temperatures Manuscript submitted for publication, 1982.

[16] 17. O'DALY, J. A.; SERRANO, L. E. & RODRIGUEZ, M. B. Free aminoacid pool and proteolytic enzymes in T. cruzi. Intern. J. Parasitology. In press.

[17] 18. RAMOS, C; SCHADTLER-SIWON, I. & ORTIZ-ORTIZ, L. Suppressor cells present in the spleens of Trypanosoma cruzi: infection mice. J. Immunol. 122: 1243-1247, 1979.

[18] 19. REED, L. J. & MUENCH, H. A simple method of estimating fifty per cent endpoints. Amer. J. Hyg. 27: 493-497, 1938.

[19] 20. REED, S. Adoptive transfer of resistance to acute Trypanosoma cruzi: infection with T-Iymphocyte-enriched spleen cells. Infect. Immun. 28: 404-410, 1980.

[20] 21. ROWLAND, E. C. & KUHN, R. E. Suppression of cellular responses in mice during Trypanosoma cruzi: infections. Infect. Immun. 20: 393-397, 1978.

[21] 22. SILVA, L. & NUSSENZWEIG, V. Sobre uma cepa de Trypanosoma cruzi: altamente virulenta para o ca-mundongo branco. Folia Clin. Biol. (São Paulo) 20: 191-208, 1953.

[22] 23. TEIXEIRA, A. R. L.; TEIXEIRA, G.; MACEDO, B. & PRATA, A. Acquired cell-mediated immunodepres-sion in acute Chagas'disease. J. Clin. Invest. 62: 1132-1141, 1978.

[23] 24. TRISCHMAN, T.; TANOWITZ, J.; WITTNER, M. & BLOOM, B. Trypanosoma cruzi: Role of the immune response in the natural resistance of inbred strains of mice. Exp. Parasitol 45: 160-168, 1978.

Brasil

Brasil

Suppression of humoral immunity and lymphocyte responsiveness during experimental trypanosoma cruzi infections

Supresión de la inmunidade humoral y de la respuesta linfocitaria durante la infección experimental con Trypanosoma cruzi

Abstracts

Publication Dates

History