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12. Antibodies to Trypanosoma cruzi express idiotypic patterns that can differentiate between patients with asymptomatic or severe Chagas' disease

Author

D Avila Reis, D., Gazzinelli, R. T., Gazzinelli, G., and Colley, D. G.

Subjects
Immunology, Immunology and Allergy
Abstract

Immunization of rabbits with pools of immunoaffinity-purified anti-Trypanosoma cruzi epimastigote antibodies derived from patients with different clinical forms of Chagas' disease induces antiidiotypic sera that can distinguish between anti-epimastigote antibodies from patients with asymptomatic (indeterminate (IND)) or severe (cardiac (CARD)) Chagas' disease. These idiotypically different anti-EPI antibodies from patients with the different clinical forms do not differ in their anti-epimastigote activities or isotypes. Analysis of immunoaffinity purified antibodies from individual chagasic patients by specific competitive ELISA generally confirms that Id-specific rabbit antisera can differentiate the clinical forms of the source of the antibodies. Based on these data, immunoaffinity-purified antibodies from patients share many Id with those from IND patients, although antibodies from IND patients express much lower levels of the distinctive Id characteristic of CARD patients. Reduction and alkylation of antibodies from IND patients reduces somewhat, but does not abolish, the ability of their Id to be recognized idiotypically, and to effectively inhibit in competitive ELISA. In contrast, reduction and alkylation of antibodies from CARD patients almost completely eliminates the ability of their predominant Id to be either recognized by, or inhibit, the appropriate systems. These data imply that the expression of the major Id that define CARD patients by these serologic anti-Id systems is largely dependent on the tertiary conformation of the Ig molecule. This agrees with our earlier studies on the respective differential abilities of CARD vs IND Id to stimulate anti-Id T cells by direct stimulation vs processing and presentation mechanisms.

Published
1993
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13. IFN-g in human Chagas' disease: protection or pathology?

Author

Bahia-Oliveira,L.M.G., Gomes,J.A.S., Rocha,M.O.C., Moreira,M.C.V., Lemos,E.M., Luz,Z.M.P., Pereira,M.E.S., Coffman,R.L., Dias,J.C.P., Cançado,J.R., Gazzinelli,G., and Corrêa-Oliveira,R.

Subjects
Chagas' disease, genetic structures, g<%2Ffont>%22">INF-g, Trypanosoma cruzi, peripheral blood mononuclear cells (PBMC), cardiomyopathy, cytokines
Abstract

An apparently paradoxical role for IFN-g in human Chagas' disease was observed when studying the pattern of cytokine production by peripheral blood mononuclear cells (PBMC) obtained from two groups of chagasic patients after specific stimulation with Trypanosoma cruzi-derived antigens. The groups studied were 1) patients treated with benznidazole during the acute phase of Trypanosoma cruzi infection and 2) chronically infected untreated patients. In the treated group, higher levels of IFN-g were produced by PBMC from individuals cured after treatment when compared to non-cured patients. In contrast, in the chronically infected group (not treated) higher levels of IFN-g were produced by PBMC from cardiac patients in comparison with asymptomatic (indeterminate) patients. This apparently paradoxical role for IFN-g in human Chagas' disease is discussed in terms of the possibility of a temporal difference in IFN-g production during the initial stages of the infection (acute phase) in the presence or absence of chemotherapy. The maintenance of an immune response with high levels of IFN-g production during the chronic phase of the infection may favor cure or influence the development of the cardiac form of the disease

Published
1998

14. IFN-<FONT FACE=Symbol>g</font> in human Chagas' disease: protection or pathology?

Author

Bahia-Oliveira, L.M.G., Gomes, J.A.S., Rocha, M.O.C., Moreira, M.C.V., Lemos, E.M., Luz, Z.M.P., Pereira, M.E.S., Coffman, R.L., Dias, J.C.P., Cançado, J.R., Gazzinelli, G., and Corrêa-Oliveira, R.

Subjects
Chagas' disease, lcsh:R5-920, genetic structures, g<%2Ffont>%22">INF-g, lcsh:Biology (General), Trypanosoma cruzi, peripheral blood mononuclear cells (PBMC), lcsh:Medicine (General), cardiomyopathy, lcsh:QH301-705.5, cytokines
Abstract

An apparently paradoxical role for IFN-g in human Chagas' disease was observed when studying the pattern of cytokine production by peripheral blood mononuclear cells (PBMC) obtained from two groups of chagasic patients after specific stimulation with Trypanosoma cruzi-derived antigens. The groups studied were 1) patients treated with benznidazole during the acute phase of Trypanosoma cruzi infection and 2) chronically infected untreated patients. In the treated group, higher levels of IFN-g were produced by PBMC from individuals cured after treatment when compared to non-cured patients. In contrast, in the chronically infected group (not treated) higher levels of IFN-g were produced by PBMC from cardiac patients in comparison with asymptomatic (indeterminate) patients. This apparently paradoxical role for IFN-g in human Chagas' disease is discussed in terms of the possibility of a temporal difference in IFN-g production during the initial stages of the infection (acute phase) in the presence or absence of chemotherapy. The maintenance of an immune response with high levels of IFN-g production during the chronic phase of the infection may favor cure or influence the development of the cardiac form of the disease

Published
1998

18. Immunological and Clinical Evaluation of Chagasic Patients Subjected to Chemotherapy during the Acute Phase ofTrypanosoma cruziInfection 14–30 Years Ago

Author

Bahia‐Oliveira, Lilian M. G., primary, Gomes, Juliana A. S., additional, Cançado, José R., additional, Ferrari, Teresa C., additional, Lemos, Elenice M., additional, Luz, Zélia M. P., additional, Moreira, Maria C., additional, Gazzinelli, G., additional, and Correa‐Oliveira, Rodrigo, additional

Published
2000
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19. T‐Cell Repertoire Analysis in Acute and Chronic Human Chagas'Disease: Differentail Frequencies of Vb5 Expressing T Cells

Author

Costa, R. P., primary, Gollob, K. J., additional, Fonseca, L. L., additional, Rocha, M. O. C., additional, Chaves, A. C. L., additional, Medrano‐Mercado, N., additional, Araújo‐Jorge, T. C., additional, Antas, P. R. Z., additional, Correa‐Oliveira, R., additional, Gazzinelli, G., additional, Carvalho‐Parra, J., additional, and Dutra, W. O., additional

Published
2000
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22. Cytokines as determinants of resistance and pathology in human Schistosoma mansoni infection

Author

Corrêa-Oliveira, R., primary, Malaquias, L.C.C., additional, Falcão, P.L., additional, Viana, I.R.C., additional, Bahia-Oliveira, L.M.G., additional, Silveira, A.M.S., additional, Fraga, L.A.O., additional, Prata, A., additional, Coffman, R.L., additional, Lambertucci, J.R., additional, Cunha-Melo, J.R., additional, Martins-Filho, O.A., additional, Wilson, R.A., additional, and Gazzinelli, G., additional

Published
1998
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23. IFN-g in human Chagas' disease: protection or pathology?

Author

Bahia-Oliveira, L.M.G., primary, Gomes, J.A.S., additional, Rocha, M.O.C., additional, Moreira, M.C.V., additional, Lemos, E.M., additional, Luz, Z.M.P., additional, Pereira, M.E.S., additional, Coffman, R.L., additional, Dias, J.C.P., additional, Cançado, J.R., additional, Gazzinelli, G., additional, and Corrêa-Oliveira, R., additional

Published
1998
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24. Evidence that cellular immune responses to soluble and membrane associated antigens are independently regulated during human schistosomiasis mansoni

Author

BAHIA-OLIVEIRA, L.M.G., primary, SIMPSON, A.J.G., additional, ALVES-OLIVEIRA, L.F., additional, CARVALHO-QUEIROZ, C., additional, SILVEIRA, A.M.S., additional, VIANA, I.R.C., additional, CUNHA-MELO, J.R., additional, HAGAN, P., additional, GAZZINELLI, G., additional, and CORREA-OLIVEIRA, R., additional

Published
1996
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39. Immune Responses during Human Schistosomiasis Mansoni.

Author

Garcia, A. A., da Silva, A. L., de Oliveira, L. R., Katz, N., Gazzinelli, G., and Colley, D. G.

Subjects
LYMPHOID tissue, LEUKOCYTES, LYMPHOCYTES, HELMINTHIASIS, LECTINS, ANTIGENS, IMMUNITY, IMMUNOGLOBULINS
Abstract

Splenocytes from 25 patients with severe hepatosplenic schistosomiasis mansoni were obtained after therapeutic splenectomy. Spleen cells were phenotyped and analysed for responsiveness lo mitogens or heterogeneous schistosome-derived antigenic preparations (eggs, SEA; adult worms. SWAP; cercariae, CERC) in blastogenesis assays and lymphokine production systems, and were compared with peripheral blood mononuclear cells (PBMN). Splenic lymphocytes were 55% T lymphocytes (sheep erythrocyte rosette-positive) and 37% surface immunoglobulin- positive B lymphocytes. The mean T4+:T8+ ratio of these sptenocytes was 1.0. Phytohaemagglutinin stimulated spleen cell production of the lymphokine mitogenic factor, but exposure to SEA or SWAP did not. Spleen cell and PBMN blastogenic responses to SEA and SWAP were sometimes, but not always in accord. Removal of plastic adherent cells allowed the non-adherent spleen cells of 30-40% of the patients to respond substantially more vigorously to SEA. SWAP and CERC, Spleen cells from a subgroup of 20-30% of the patients failed to respond to the schistosomal antigens regardless of removal of adherent cells. Spleen cell responses to gram-negative lipopolysaccharide peaked on day 5 or 6 of culture, and were augmented by adherent cell removal, Pokeweed mitogen-stimulated responses were optimal on day 5 of culture. Spleen cells from most severe, hepatosplenic schistosomiasis mansoni patients do not respond well to schistosomal antigens or B-cell mitogens. The splenic responses of many of these patients were elevated by the removal of adherent spleen cells. [ABSTRACT FROM AUTHOR]

Published
1986
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40. Immune Responses during Human Schistosomiasis Mansoni IX. T-Lymphocyte Subset Analysis by Monoclonal Antibodies in Hepatosplenic Disease.

Author

Colley, D. G., Katz, N., Rocha, R. S., Abrantes, W., da Silva, A. L., and Gazzinelli, G.

Subjects
T cells, LYMPHOCYTES, MONOCLONAL antibodies, IMMUNOGLOBULINS, IMMUNE response
Abstract

T lymphocyte immunoregulatory subsets (T4+ and T8+ cells) have been analysed in eight cases or hepatosplenic schistosomiasis mansoni, and compared to parallel analyses of seven intestinal Schistosoma mansoni infected patients and four uninfected control subjects. The mean T4+ : T8+ ratio in hepatosplenic cases was markedly loss than observed in other groups (0.94 vs 1.86 vs 2.22, respectively). Proliferative responses stimulated by a soluble adult worm extract correlated directly with the observed T4 :T8 ratios. Normal levels of E rosette-positive and surface immunoglobulin-bearing lymphoid cells were observed in intestinal patients, while hepatosplenic patients demonstrated normal B lymphocyte proportions but highly erratic E rosette-positive percentages. Curiously, in hepatosplenic patients the percentage of E rosette-positive cells often did not correlate with the proportion of T3+ cells. [ABSTRACT FROM AUTHOR]

Published
1983
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41. Clinical forms of human Schistosoma mansoni infection are associated with differential activation of T-cell subsets and costimulatory molecules.

Author

Martins-Filho, Olindo, Cunha-Melo, Jose, Lambertucci, Jose, Silveira, Alda, Colley, Daniel, Gazzinelli, Giovanni, Correa-Oliveira, Rodrigo, Martins-Filho, O A, Cunha-Melo, J R, Lambertucci, J R, Silveira, A M, Colley, D G, Gazzinelli, G, and Correa-Oliveira, R

Abstract

The current study has compared the activation status and the expression of the CD28 molecule on circulating CD4+ and CD8+ lymphocytes from patients with different clinical forms of schistosomiasis. The data show that patients with acute schistosomiasis have an increase on the mean percentage of CD4+ HLA-DR+ cells, whereas chronic asymptomatic patients exhibit an increased mean percentage of CD8+ HLA-DR+ cells. Patients with the hepatosplenic disease showed an increase in both CD4+ HLA-DR+ and CD8+ HLA-DR+ cells. Despite the high levels of CD8+ HLA-DR+ cells in hepatosplenic patients, they presented a decreased ratio of CD8+ CD28+/CD8+ cells. These findings of a different percentage of circulating CD8+ CD28+ cells might explain the different in vitro cellular reactivity of asymptomatic and hepatosplenic patients and the defects in the cytokine secretion patterns reported in individuals with hepatosplenic schistosomiasis. [ABSTRACT FROM AUTHOR]

Published
1999
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50. Anti-Trypanosoma cruzi and anti-laminin antibodies in chagasic patients after specific treatment

Author

Gazzinelli, R T, Galvão, L M, Cardoso, J E, Cançado, J R, Krettli, A U, Brener, Z, and Gazzinelli, G

Abstract

The antibody response to Trypanosoma cruzi epimastigote and trypomastigote stages, as well as to laminin, was studied in several groups of chagasic patients. In six patients who were cured of the parasite, the serum antibody titers as revealed by indirect immunofluorescence and hemagglutination tests against epimastigotes (conventional serology) and a complement-mediated lysis test with living trypomastigotes did not differ from those of normal individuals. In seven presumably cured patients, although the complement-mediated lysis test turned negative, conventional serology remained positive. Sera from this group of so-called "dissociated" patients presented significant lower mean antibody titers against epimastigote but not trypomastigote stages than did sera from 14 untreated patients (P less than 0.01). Most of the antibodies against trypomastigotes, including the residual levels found in cured patients, were absorbed by mouse laminin. In fact, significantly higher titers of anti-laminin antibodies were observed in sera from untreated chagasic patients (1.131 +/- 0.458) and cured patients (1.103 +/- 0.572) than in sera from eight normal individuals (0.459 +/- 0.402) (P less than 0.01). The anti-laminin titers were higher in sera of patients of blood group A or O than in those of patients of group B or AB. In Western blotting (immunoblotting) analysis against trypomastigotes, sera from chronic untreated patients recognized many polypeptide bands ranging from 26 to 160 kilodaltons, whereas no protein bands were observed with sera from cured patients. Only faint bands of parasite proteins were observed with sera of dissociated patients. In conjunction, the above data suggest that the anti-trypomastigote antibodies which persist after parasitological cure of patients with Chagas' disease are due mainly to cross-reactive epitopes from mouse laminin.

Published
1988
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