Interferon gamma production by PAS-positive T lymphocytes of chagasic patients infiltrated into human hearts in the sites of lesions.

UNLABELLED: In the blood of chagasic patients, a high number of T-lymphocytes producers of a PA.S.-positive substance was found, more numerous in chagasics with abnormal electrocardiogram. Further, we found such lymphocytes infiltrated in the chagasic heart. Here, we considered our hypothesis that those lymphocytes would be Interferon -gamma producer' cells. MATERIAL AND METHODS: Heart samples of 8 patients deceased due to chagasic heart disease (ChHD). Cuts of 5 microns were submitted to monoclonal antibodies for human Interferon-gamma; to CD45RO for activated T lymphocytes; and to the classical Periodic acid Schiff reaction (P.A.S.), respectively. In blood smears from chagasic patients with ChHD, the reactivity for anti Interferon gamma and for the P.A.S. reaction was compared, regarding the respective positive cell number. The myocardium status was compared with clinical date. RESULTS: In hearts, 65-75% of infiltrated lymphocytes were positive for IFN-gamma; similar values were found , in seriated cuts, of P.A.S.-positive lymphocytes, as well as of CD45RO+. In blood, there were 41%+/-9 of P.A.S.-positive lymphocytes, similar to positive cells for IFN-gamma. CONCLUSIONS: The data indicates that the P.A.S.-positive lymphocytes from chagasic patients are producers of IFN-gamma in blood, as well as when infiltrated into the cardiac tissues. Such fact explains also the great affluence of macrophages in cardiac tissues in ChHD. The data indicate a strong response of T helper 1 type in this severe advanced stage of Chagas'disease. Neither Typanosome cruzi parasites or intracellular forms were seen in these hearts. This favors the data showing autoimmune mechanisms in this process. We open a question: to which antigen/s respond in the chagasic hearts the lymphocytes producers of IFN-gamma?

Neomicrovasculatura: factor activo en la inmunopatogenia de la cardiopatía chagásica crónica / Neo-microvasculature: an active factor in the immunopathogenesis of chronic chagasic cardiopathy

Jõrg demostró reducción del lecho capilar en el corazón chagásico. Después, Cabral y colaboradores hallaron vénulas de endotelio alto (VEA), que normalmente sólo existen en tejidos linfáticos. Aquí estudiamos nuevos aspectos sobre neomicrovasos en la cardiopatía chagásica crónica (CChC) con muerte cardíaca. Estudiamos muestras de corazones de pacientes que murieron a una edad media de 41 años (n = 8) y otros con muerte a una edad media de 62 años (n = 9). Se estudiaron cortes de 5 micrones con coloraciones clásicas y otros con anticuerpos monoclonales e inmunocitoquímica, para células y vasos. Los neovasos-vénulas se contaron a una magnificación Î400, en 50 campos. Resultados: En todos los casos se hallaron VEA. Los corazones con muerte más temprana tuvieron un número mayor de VEA y otras vénulas, de endotelio plano (4,1 ± 1,3 versus 1,2 ± 0,3, por campo) (p< 0,001) con respecto a los corazones con muerte tardía. Ambos tipos de microvasos, cuyo diámetro fue de 25 a 90 micrones, mostraron linfocitos (CD45RO+) y macrófagos (CD68+) en su interior y saliendo hacia el intersticio cardíaco. Mediante anticuerpos anti-CD31 o bien ICAM-1/CD54 se demostró inmunotinción de endotelios y de células con anti-CD44. No se observó T. cruzi. Los datos muestran que en el corazón chagásico se producen modificaciones de la microvasculatura con producción de neomicrovasos venulares que permiten un tránsito linfocitario-macrofágico intenso hacia los tejidos cardíacos y refuerzan los datos que sugieren autoinmunidad en el proceso chagásico. Su mayor cantidad, neomicrovasos e inmunocitos, se asoció con un número más alto de arritmias malignas y muerte temprana. Abrimos la pregunta: ¿qué llevan a su producción?

[Chagas cardiopathy: identification and quantification of infiltrating cells in the hearts of cardiac death patients of different ages]. / Cardiopatía chagasica: identificación y cuantificación de células infiltrantes, en corazones de pacientes que sufrieron muerte cardíaca a distintas edades.

UNLABELLED: The purpose of this work was to obtain new data on factors intervening in the production and progression of human chagasic cardiopathy (HChC) with death by cardiac failure. We studied cardiac samples of patients that died at an early mean age versus others that died at older ages. The infiltrating cells were characterized and quantified by means of specific monoclonal antibodies and inmunohistochemical methodology; and by classical histological and histochemical methods. We found intense cardiac infiltration by lymphocytes that reacted with the antibodies anti-CD45RO against activated T-lymphocytes (< 70%). A similar number showed reactivity for CD4. And, in seriate sections, showed PAS+ substances in their cytoplasms. Macrophages were detected in a number of 25%. Few lymphocytes reacted to CD8. There was a low number of B lymphocytes. Other noticeable infiltrated cell were intramiocardial mast cells. Qualitatively, such findings were similar in the two groups of patients. However, the number of T-lymphocytes and of the mast cells was significantly higher in the cases that underwent early cardiac death (p < 0.001). T. cruzi was not found. In cardiomyocytes, damages were found, with T-lymphocytes and macrophages adhered to their sarcolemma, as well as mast cells. CONCLUSIONS: These findings suggest the existence of an active and intense occurrence of immunocellular mechanisms in the production and evolution of severe HChC, in which T-lymphocytes CD4+ intervene, with production and secretion of PAS+ substances; Besides, macrophages, and mast cells, in that order. The quantity of infiltrated cells was positively associated with the occurrence of malignant arrythmyias. We suggest that such facts would be involved in the poor cardiac performance of the chagasic heart disease that leads to cardiac death. Indeed, they seem be worthy of consideration with respect to therapeutic strategies.

Cardiopatía chagasica: identificación y cuantificación de células infiltrantes, en corazones de pacientes que sufrieron muerte cardíaca a distintas edades. / [Chagas cardiopathy: identification and quantification of infiltrating cells in the hearts of cardiac death patients of different ages]

The purpose of this work was to obtain new data on factors intervening in the production and progression of human chagasic cardiopathy (HChC) with death by cardiac failure. We studied cardiac samples of patients that died at an early mean age versus others that died at older ages. The infiltrating cells were characterized and quantified by means of specific monoclonal antibodies and inmunohistochemical methodology; and by classical histological and histochemical methods. We found intense cardiac infiltration by lymphocytes that reacted with the antibodies anti-CD45RO against activated T-lymphocytes (< 70

). A similar number showed reactivity for CD4. And, in seriate sections, showed PAS+ substances in their cytoplasms. Macrophages were detected in a number of 25

. Few lymphocytes reacted to CD8. There was a low number of B lymphocytes. Other noticeable infiltrated cell were intramiocardial mast cells. Qualitatively, such findings were similar in the two groups of patients. However, the number of T-lymphocytes and of the mast cells was significantly higher in the cases that underwent early cardiac death (p < 0.001). T. cruzi was not found. In cardiomyocytes, damages were found, with T-lymphocytes and macrophages adhered to their sarcolemma, as well as mast cells. CONCLUSIONS: These findings suggest the existence of an active and intense occurrence of immunocellular mechanisms in the production and evolution of severe HChC, in which T-lymphocytes CD4+ intervene, with production and secretion of PAS+ substances; Besides, macrophages, and mast cells, in that order. The quantity of infiltrated cells was positively associated with the occurrence of malignant arrythmyias. We suggest that such facts would be involved in the poor cardiac performance of the chagasic heart disease that leads to cardiac death. Indeed, they seem be worthy of consideration with respect to therapeutic strategies.