Lymphocyte subpopulations and neutrophil function in chronic human Chagas' disease

Voltarelli, J. C.; Donadi, E. A.; Carvalho, I. F.; Falcão, R. P.

doi:10.1590/S0036-46651990000400002

Abstracts

The absolute numbers of total leukocytes, lymphocytes, T cells, helper/inducer, suppressor/cytotoxic and B cells were decreased in the peripheral blood of patients with chronic Chagas' disease. Since antilymphocyte antibodies were present only in a minority of patients they probably cannot account for the abnormalities in lymphocyte subsets. Patient neutrophils stimulated with endotoxin-treated autologous plasma showed depressed chemotactic activity and this seems to be an intrinsic cellular defect rather than plasma inhibition. Random migration of neutrophils was normal. Reduction of nitroblue tetrazolium by endotoxin- stimulated neutrophils was also decreased. These findings further document the presence of immunosuppression in human Chagas' disease. They may be relevant to autoimmunity, defense against microorganisms and against tumor cells at least in a subset of patients with more severe abnormalities.

Chagas' disease; Leukopenia; Lymphopenia; lymphocyte subpopulations; Chemotaxis; NBT test; Antilymphocyte antibodies

Números absolutos de leucócitos e linfócitos, de células T totais, indutoras/auxiliares, supressoras/citotóxicas e de células B estavam diminuídos no sangue periférico de pacientes com doença de Chagas crônica. Como anticorpos antilinfocitários estavam presentes em apenas uma minoria de pacientes, eles provavelmente não são responsáveis pelas anormalidades das subpopulações de linfócitos. Neutrófilos de pacientes estimulados por plasma autólogo tratado por endotoxina mostravam atividade quimiotática diminuída que deve ser devida a um defeito celular intrínseco e não a inibição plasmática. A migração aleatória dos neutrófilos estava normal. A redução do corante "nitroblue tetrazolium" (NBT) por neutrófilos estimulados por endotoxina também estava diminuída nos pacientes. Estes achados estendem a documentação da imunossupressão na doença de Chagas humana. Eles podem ser relevantes para autoimunidade e para defesa contra microorganismos e células tumoráis, pelo menos em um subgrupo de pacientes com anormalidades mais pronunciadas.

ORIGINAL ARTICLES

Lymphocyte subpopulations and neutrophil function in chronic human Chagas' disease

Subpopulações linfocitárias e função neutrofílica na doença de Chagas humana

J. C. Voltarelli; E. A. Donadi; I. F. Carvalho; R. P. Falcão

Department of Clinical Medicine, School of Medicine, Ribeirão Preto, Brazil

^{Address for correspondence} Address for correspondence: Dr. Julio C. Voltarelli Department of Clinical Medicine, School of Medicine 14049 Ribeirão Preto, São Paulo, Brazil Tel. (016) 6331000 Ext. 2315

SUMMARY

The absolute numbers of total leukocytes, lymphocytes, T cells, helper/inducer, suppressor/cytotoxic and B cells were decreased in the peripheral blood of patients with chronic Chagas' disease. Since antilymphocyte antibodies were present only in a minority of patients they probably cannot account for the abnormalities in lymphocyte subsets. Patient neutrophils stimulated with endotoxin-treated autologous plasma showed depressed chemotactic activity and this seems to be an intrinsic cellular defect rather than plasma inhibition. Random migration of neutrophils was normal. Reduction of nitroblue tetrazolium by endotoxin- stimulated neutrophils was also decreased. These findings further document the presence of immunosuppression in human Chagas' disease. They may be relevant to autoimmunity, defense against microorganisms and against tumor cells at least in a subset of patients with more severe abnormalities.

Key words: Chagas' disease; Leukopenia; Lymphopenia; lymphocyte subpopulations; Chemotaxis; NBT test; Antilymphocyte antibodies.

RESUMO

Números absolutos de leucócitos e linfócitos, de células T totais, indutoras/auxiliares, supressoras/citotóxicas e de células B estavam diminuídos no sangue periférico de pacientes com doença de Chagas crônica. Como anticorpos antilinfocitários estavam presentes em apenas uma minoria de pacientes, eles provavelmente não são responsáveis pelas anormalidades das subpopulações de linfócitos. Neutrófilos de pacientes estimulados por plasma autólogo tratado por endotoxina mostravam atividade quimiotática diminuída que deve ser devida a um defeito celular intrínseco e não a inibição plasmática. A migração aleatória dos neutrófilos estava normal. A redução do corante "nitroblue tetrazolium" (NBT) por neutrófilos estimulados por endotoxina também estava diminuída nos pacientes. Estes achados estendem a documentação da imunossupressão na doença de Chagas humana. Eles podem ser relevantes para autoimunidade e para defesa contra microorganismos e células tumoráis, pelo menos em um subgrupo de pacientes com anormalidades mais pronunciadas.

Full text available only in PDF format.

Texto completo disponível apenas em PDF.

ACKNOWLEDGMENTS

The authors are grateful to Mrs. Agalir B. Garcia, Maria Inez S. Ancheschi and Maria Perpétua F. Moraes for technical assistance, to Dr. Marvin R. Garovoy and Mrs. Cassia M. C. Monteiro for helping with the antilymphocyte antibody techniques, to Dr. Ken Kopecky for statistical advice, to Drs. Lewis J. Greene and Daniel P. Stites for reviewing the manuscript and to Ms. Lucia H. G. Teixeira for helping in preparing the manuscript. This work was supported by CNPq (Proc. 301465/79 CL-07, 405023/84, 405319/BM/FV and 301584/87-7).

Recebido para publicação em 24/7/1989.

1. ABATH, F.G.C.; MONTENEGRO, S.M.L. & CARVALHO, A.B. In vivo leukocyte chemotaxis during the development of acute experimental Trypanosoma cruzi infection. Braz. J. med. biol. Res., 21: 1013-1014, 1988.
2. AKENZUA, G.I. & AMIENGHEME, O.R. Inhibitor of in vitro neutophil migration in sera of children with homozygous sikle cell gene during pain crisis. Brit. J. Haemat., 47: 345-352, 1981.
3. AMOS, D.B.; BASHIR, H.; BOYLE, W.; McQUEEN, M. & TILIKAINEN, A.A. A simple microcytotoxicity test. Transplantation, 7: 220-222, 1969.
4. BOTASSO, O.A.; MANGITERRA, L.; LUNA, M.B.; AMERIO, N. & MORINI, J.C. Perfil immunológico en pacientes con enfermedad de Chagas cronica. Medicina (B. Aires), 42: 136-140, 1982.
5. BOYUM, A. Isolation of mononuclear cells and granulocytes from human blood. Scand. J. clin. Lab. Invest., 21 (suppl. 97): 77-89, 1968.
6. CARDONI, R.L.; DOCAMPO, R. & CASELLAS, A.M. Metabolic requirements for the damage of Trypanosoma cruzi epimastigotes by polymorphonuclear leukocytes. J. Parasit., 68: 547-552, 1982.
7. CORSINI, A.C. Immune dysfunction in animals with experimental trypanosomiasis. Afr. J. clin. exp. Immunol., 3: 107-118. 1982.
8. CORSINI, A.C.; VILELA, M.M.S. & PIEDRABUENA, A.E. Chronic Chagas' disease: unimpaired delayed type hypersensitivity reaction in contrast with humoral supression to typhoid vaccine. Tropenmed. Parasit., 32: 82-86, 1981.
9. CUNNINGHAM, D.S.; BENEVIDES, G.R. & KUHN, R.E. Differences in the regulation of humoral responses between mice infected with Trypanosoma cruzi and mice administered T. cruzi induced suppressor substance. J. Immunol., 125: 2317-2321, 1980.
10. CUNNINGHAM, D.S.; GROGL, M. & KUHN, R.E. Suppression of antibody responses in humans infected with Trypanosoma cruzi. Infect., Immun., 30: 496-499, 1980.
11. DIEZ, R.A.; ESTEVES, M.E.; SEN, L.; BAROUSSE, A.P. & LEPLUME, H. Alteraciones de la funcion litica en las celulas fagociticas en la enfermidad de Chagas. Medicina (B. Aires), 40: 812, 1980.
12. FALCÃO, R.P.; VOLTARELLI, J.C. & BOTTURA, C. The role of the spleen on the reduction of nitroblue tetrazolium by neutrophils. Acta Haematol., 68: 89-95, 1982.
13. FERREIRA, G.G.; ARGUELES, E. & OLIVEIRA-LIMA, A. Depression of blood monocytes chemotaxis in human chronic Chagas disease. Rev. Inst. Med. trop. S. Paulo, 21: 297-301, 1979.
14. GAROVOY, M.R.; RHEINSCHMIDT, M.A.; BIGOS, M.; PERKINS, H.; COLOMBE, B.; TEDRISKA, M. & SALVATIERRA, O. Flow cytrometry analysis: A high technology crossmatch technique facilitating transplantation. Transplant. Proc., 15: 1939-1944, 1983.
15. GATASS, C.R.; ALBANESI FILHO, F.M. & BARCINSKI, M.A. Lymphocyte subpopulations in chronic Chagas disease. Immunol. Lett., 8: 289-292, 1974.
16. JAYAWARDENA, A.N.; WASKMAN, B.A. & EARDLEY, D.D. Activation of distinct helper and suppressor T cells in experimental trypanosomiasis. J. Immunol., 121: 622-628, 1978.
17. KIERSZENBAUM, F. Antibody dependent killing of bloodstream forms of Trypanosoma cruzi by human peripheral blood leukocytes. Amer. J. trop. Med. Hyg., 28: 965-968, 1979.
18. KIERSZENBAUM, F. & HAYES, M.M. Mechanisms of resistance against experimental Trypanosoma cruzi infection. Requeriments for cellular destruction of circulating forms of T. cruzi in human and murine in vitro systems. Immunology, 40: 61-66, 1980.
19. KIMACHI, T.; LOMONACO, D.A. & VERISSIMO, J.M.T. Exploraçăo funcional do eixo hipotalamo-hipofise-cortex adrenal na forma crônica da moléstia de Chagas. Rev. Ass. méd. bras., 20: 57-66, 1974.
20. LELCHUCK, R. CARDONI, R.L. & FUKS, A.S. Cell mediated immunity in Chagas' diesease. Alterations induced by treatment with trypanocidal drug (nifurtimox). Clin. exp. Immunol., 30: 434-438, 1977.
21. LEVINSON, S.S. & GOLDMAN, J. Measurement of circulating Clq precipitable immune complexes by a nephelometric type assay after polyethylene glycol extraction in model system. Amer. J. clin. Path., 79: 451-457, 1983.
22. LUSTING, S.E.; PURICELLI, L.; BAL, E. & LANCETTI, J.C. Association of Chagas disease and cancer. Medicina (B. Aires), 40: 43-46, 1980.
23. MADEIRA, E.D.; ANDRADE, A.F.B.; BRUNN-MORENO, M.M. & BARCINSKI, M. Antibody-dependent cellular cytotoxicity of Trypanosoma cruzi: Characterization of the effector cell from normal human blood. Infect. Immun., 25: 34-38, 1979.
24. MENDES, N.F.; PEIXINHO, Z.F.; MOIRA, M.C. & CAMARGO, E.P. Cross-reactions between Trypanosomatidae cell extracts and HLA antigens. Trnsplant. Proc., 11: 1304-1305, 1979.
25. MONTUFAR, O.M.B.; MUSATTI, C.C.; MENDES, E. & MENDES, N.F. Cellular immunity in chronic Chagas disease. J. clin. Microbiol., 5: 401-404, 1977.
26. O' DALY, J.A.; SIMONIS, S.; ROLO, N. de & CABALLERO, H. Suppression of humoral immunity and lymphocyte responsiveness during experimental Trypanosoma cruzi infections. Rev. Inst. Med. trop. S. Paulo, 26: 67-77, 1984.
27. OLABUENAGA, S.E.; RIMOLDI, M.T.; CARDONI, R.L.; RIERA, N.E.; SANCHEZ, R.A.; CHIALE, P. & DE BRACCO, M.M.E. Actividad citotoxica de leucocitos de pacientes chagasicos cronicos contra Trypanosoma cruzi. Medicina (B. Aires), 43: 168-174, 1983.
28. PLATA, F. Enhancement of tumor growth correlates with suppression of the tumor specific cytolytic T lymphocyte response in mice chronically infected by Trypanosoma cruzi. J. Immunol., 134: 1312-1319, 1985.
29. REZENDE, J.M. Clínica: Manifestaçőes digestivas. In: BRENER, Z. & ANDRADE, Z. ed. Trypanosoma cruzi e Doença de Chagas. Rio de Janeiro, Guanabara Koogan, 1979. p. 312-361.
30. RIMOLDI, M.T.; CARDONI, R.L.; OLABUENAGA, S.E. & DE BRACCO, M.M.E. Trypanosoma cruzi: Sequence of phagocytosis and cytotoxicity by human polymorphonuclear leukocytes. Immunology, 42: 521-527, 1981.
31. SANDERSON, C.J. & SOUZA, M.
32. SANTOS BUCH, C.A. & TEIXEIRA, A.R.L. - The immunology of experimental Chagas disease. III. Rejection of allogeneic heart cells in vitro. J. exp. Med., 140: 38-53, 1974.
33. TEIXEIRA, A.R.L.; TEIXEIRA, G.; MACHADO, V. & PRATA, A. Acquired cell mediated immunodepression in acute Chagas disease. J. clin. Invest., 62: 1132-1141, 1978.
34. VILALTA, F. & KIERSZENBAUM, F. Role of polymorphonuclear cells in Chagas disease. II. Uptake and mechanisms of destruction of intracellular (amastigote) forms of Trypanosoma cruzi by human neutrophils. J. Immunol., 131: 1504-1510, 1983.
35. VOLTARELLI, J.C.; DONADI, E.A. & FALCĂO, R.P. Immunosuppression in human acute Chagas disease. Trans. roy. Soc. trop. Med. Hyg., 81: 169-170, 1987.
36. VOLTARELLI, J.C.; FALCĂO, R.P. & SANTANA DA SILVA, J. Antibody-dependent cellular cytotoxicity in chronic human Chagas disease. Parasite Immunol., 5: 377-384, 1983.
37. ZIGMOND, S.H. & HIRSCH, J.G. Leukocyte locomotion and chemotaxis. New methods for evaluation and demonstration of a cell-derived chemotactic factor. J. exp. Med., 137: 387-410, 1973.
38. ZUBLER, R.H.; PERRIN, L.H.; CREIGHTON, W.D. & LAMBERT, P.H. Use of polyethylene glycol (PEG) to concentrate immune complexes from serum or plasma samples. Ann. rheum. Dis., 36 (Suppl. 1): 23-30, 1977.

Address for correspondence:

Dr. Julio C. Voltarelli

Department of Clinical Medicine, School of Medicine

14049 Ribeirão Preto, São Paulo, Brazil

Tel. (016) 6331000 Ext. 2315

Publication Dates

Publication in this collection
12 Sept 2006
Date of issue
Aug 1990

History

Received
24 July 1989

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

[1] 1. ABATH, F.G.C.; MONTENEGRO, S.M.L. & CARVALHO, A.B. In vivo leukocyte chemotaxis during the development of acute experimental Trypanosoma cruzi infection. Braz. J. med. biol. Res., 21: 1013-1014, 1988.

[2] 2. AKENZUA, G.I. & AMIENGHEME, O.R. Inhibitor of in vitro neutophil migration in sera of children with homozygous sikle cell gene during pain crisis. Brit. J. Haemat., 47: 345-352, 1981.

[3] 3. AMOS, D.B.; BASHIR, H.; BOYLE, W.; McQUEEN, M. & TILIKAINEN, A.A. A simple microcytotoxicity test. Transplantation, 7: 220-222, 1969.

[4] 4. BOTASSO, O.A.; MANGITERRA, L.; LUNA, M.B.; AMERIO, N. & MORINI, J.C. Perfil immunológico en pacientes con enfermedad de Chagas cronica. Medicina (B. Aires), 42: 136-140, 1982.

[5] 5. BOYUM, A. Isolation of mononuclear cells and granulocytes from human blood. Scand. J. clin. Lab. Invest., 21 (suppl. 97): 77-89, 1968.

[6] 6. CARDONI, R.L.; DOCAMPO, R. & CASELLAS, A.M. Metabolic requirements for the damage of Trypanosoma cruzi epimastigotes by polymorphonuclear leukocytes. J. Parasit., 68: 547-552, 1982.

[7] 7. CORSINI, A.C. Immune dysfunction in animals with experimental trypanosomiasis. Afr. J. clin. exp. Immunol., 3: 107-118. 1982.

[8] 8. CORSINI, A.C.; VILELA, M.M.S. & PIEDRABUENA, A.E. Chronic Chagas' disease: unimpaired delayed type hypersensitivity reaction in contrast with humoral supression to typhoid vaccine. Tropenmed. Parasit., 32: 82-86, 1981.

[9] 9. CUNNINGHAM, D.S.; BENEVIDES, G.R. & KUHN, R.E. Differences in the regulation of humoral responses between mice infected with Trypanosoma cruzi and mice administered T. cruzi induced suppressor substance. J. Immunol., 125: 2317-2321, 1980.

[10] 10. CUNNINGHAM, D.S.; GROGL, M. & KUHN, R.E. Suppression of antibody responses in humans infected with Trypanosoma cruzi. Infect., Immun., 30: 496-499, 1980.

[11] 11. DIEZ, R.A.; ESTEVES, M.E.; SEN, L.; BAROUSSE, A.P. & LEPLUME, H. Alteraciones de la funcion litica en las celulas fagociticas en la enfermidad de Chagas. Medicina (B. Aires), 40: 812, 1980.

[12] 12. FALCÃO, R.P.; VOLTARELLI, J.C. & BOTTURA, C. The role of the spleen on the reduction of nitroblue tetrazolium by neutrophils. Acta Haematol., 68: 89-95, 1982.

[13] 13. FERREIRA, G.G.; ARGUELES, E. & OLIVEIRA-LIMA, A. Depression of blood monocytes chemotaxis in human chronic Chagas disease. Rev. Inst. Med. trop. S. Paulo, 21: 297-301, 1979.

[14] 14. GAROVOY, M.R.; RHEINSCHMIDT, M.A.; BIGOS, M.; PERKINS, H.; COLOMBE, B.; TEDRISKA, M. & SALVATIERRA, O. Flow cytrometry analysis: A high technology crossmatch technique facilitating transplantation. Transplant. Proc., 15: 1939-1944, 1983.

[15] 15. GATASS, C.R.; ALBANESI FILHO, F.M. & BARCINSKI, M.A. Lymphocyte subpopulations in chronic Chagas disease. Immunol. Lett., 8: 289-292, 1974.

[16] 16. JAYAWARDENA, A.N.; WASKMAN, B.A. & EARDLEY, D.D. Activation of distinct helper and suppressor T cells in experimental trypanosomiasis. J. Immunol., 121: 622-628, 1978.

[17] 17. KIERSZENBAUM, F. Antibody dependent killing of bloodstream forms of Trypanosoma cruzi by human peripheral blood leukocytes. Amer. J. trop. Med. Hyg., 28: 965-968, 1979.

[18] 18. KIERSZENBAUM, F. & HAYES, M.M. Mechanisms of resistance against experimental Trypanosoma cruzi infection. Requeriments for cellular destruction of circulating forms of T. cruzi in human and murine in vitro systems. Immunology, 40: 61-66, 1980.

[19] 19. KIMACHI, T.; LOMONACO, D.A. & VERISSIMO, J.M.T. Exploraçăo funcional do eixo hipotalamo-hipofise-cortex adrenal na forma crônica da moléstia de Chagas. Rev. Ass. méd. bras., 20: 57-66, 1974.

[20] 20. LELCHUCK, R. CARDONI, R.L. & FUKS, A.S. Cell mediated immunity in Chagas' diesease. Alterations induced by treatment with trypanocidal drug (nifurtimox). Clin. exp. Immunol., 30: 434-438, 1977.

[21] 21. LEVINSON, S.S. & GOLDMAN, J. Measurement of circulating Clq precipitable immune complexes by a nephelometric type assay after polyethylene glycol extraction in model system. Amer. J. clin. Path., 79: 451-457, 1983.

[22] 22. LUSTING, S.E.; PURICELLI, L.; BAL, E. & LANCETTI, J.C. Association of Chagas disease and cancer. Medicina (B. Aires), 40: 43-46, 1980.

[23] 23. MADEIRA, E.D.; ANDRADE, A.F.B.; BRUNN-MORENO, M.M. & BARCINSKI, M. Antibody-dependent cellular cytotoxicity of Trypanosoma cruzi: Characterization of the effector cell from normal human blood. Infect. Immun., 25: 34-38, 1979.

[24] 24. MENDES, N.F.; PEIXINHO, Z.F.; MOIRA, M.C. & CAMARGO, E.P. Cross-reactions between Trypanosomatidae cell extracts and HLA antigens. Trnsplant. Proc., 11: 1304-1305, 1979.

[25] 25. MONTUFAR, O.M.B.; MUSATTI, C.C.; MENDES, E. & MENDES, N.F. Cellular immunity in chronic Chagas disease. J. clin. Microbiol., 5: 401-404, 1977.

[26] 26. O' DALY, J.A.; SIMONIS, S.; ROLO, N. de & CABALLERO, H. Suppression of humoral immunity and lymphocyte responsiveness during experimental Trypanosoma cruzi infections. Rev. Inst. Med. trop. S. Paulo, 26: 67-77, 1984.

[27] 27. OLABUENAGA, S.E.; RIMOLDI, M.T.; CARDONI, R.L.; RIERA, N.E.; SANCHEZ, R.A.; CHIALE, P. & DE BRACCO, M.M.E. Actividad citotoxica de leucocitos de pacientes chagasicos cronicos contra Trypanosoma cruzi. Medicina (B. Aires), 43: 168-174, 1983.

[28] 28. PLATA, F. Enhancement of tumor growth correlates with suppression of the tumor specific cytolytic T lymphocyte response in mice chronically infected by Trypanosoma cruzi. J. Immunol., 134: 1312-1319, 1985.

[29] 29. REZENDE, J.M. Clínica: Manifestaçőes digestivas. In: BRENER, Z. & ANDRADE, Z. ed. Trypanosoma cruzi e Doença de Chagas. Rio de Janeiro, Guanabara Koogan, 1979. p. 312-361.

[30] 30. RIMOLDI, M.T.; CARDONI, R.L.; OLABUENAGA, S.E. & DE BRACCO, M.M.E. Trypanosoma cruzi: Sequence of phagocytosis and cytotoxicity by human polymorphonuclear leukocytes. Immunology, 42: 521-527, 1981.

[31] 31. SANDERSON, C.J. & SOUZA, M.

[32] 32. SANTOS BUCH, C.A. & TEIXEIRA, A.R.L. - The immunology of experimental Chagas disease. III. Rejection of allogeneic heart cells in vitro. J. exp. Med., 140: 38-53, 1974.

[33] 33. TEIXEIRA, A.R.L.; TEIXEIRA, G.; MACHADO, V. & PRATA, A. Acquired cell mediated immunodepression in acute Chagas disease. J. clin. Invest., 62: 1132-1141, 1978.

[34] 34. VILALTA, F. & KIERSZENBAUM, F. Role of polymorphonuclear cells in Chagas disease. II. Uptake and mechanisms of destruction of intracellular (amastigote) forms of Trypanosoma cruzi by human neutrophils. J. Immunol., 131: 1504-1510, 1983.

[35] 35. VOLTARELLI, J.C.; DONADI, E.A. & FALCĂO, R.P. Immunosuppression in human acute Chagas disease. Trans. roy. Soc. trop. Med. Hyg., 81: 169-170, 1987.

[36] 36. VOLTARELLI, J.C.; FALCĂO, R.P. & SANTANA DA SILVA, J. Antibody-dependent cellular cytotoxicity in chronic human Chagas disease. Parasite Immunol., 5: 377-384, 1983.

[37] 37. ZIGMOND, S.H. & HIRSCH, J.G. Leukocyte locomotion and chemotaxis. New methods for evaluation and demonstration of a cell-derived chemotactic factor. J. exp. Med., 137: 387-410, 1973.

[38] 38. ZUBLER, R.H.; PERRIN, L.H.; CREIGHTON, W.D. & LAMBERT, P.H. Use of polyethylene glycol (PEG) to concentrate immune complexes from serum or plasma samples. Ann. rheum. Dis., 36 (Suppl. 1): 23-30, 1977.

Brasil

Brasil

Lymphocyte subpopulations and neutrophil function in chronic human Chagas' disease

Subpopulações linfocitárias e função neutrofílica na doença de Chagas humana

Abstracts

Address for correspondence:

Publication Dates

History