RESUMEN
Human chronic Chagas disease cardiomyopathy (CCC) is an inflammatory-dilated cardiomyopathy occurring years after infection by the protozoan Trypanosoma cruzi. The heart inflammatory infiltrate in CCC shows a 2:1 predominance of CD8(+) in relation to CD4(+) T cells, with a typical Th1-type cytokine profile. However, in vitro expansion of infiltrating T cells from heart biopsy-derived fragments with interleukin-2 (IL-2) and phytohaemagglutinin leads to the outgrowth of CD4(+) over CD8(+) T cells. We hypothesized that survival cytokines, such as IL-2, IL-7 and IL-15 might be differentially involved in the growth and maintenance of heart-infiltrating and peripheral CD8(+) T cells from CCC patients. We found that IL-7 and IL-15 were superior to IL-2 in the expansion and viability of CD8(+) T cells from both PBMC and heart-infiltrating T-cell lines from CCC patients, and the combination of the three cytokines showed synergic effects. Heart-infiltrating CD8(+) T cells showed higher expression of both IL-15R alpha and gamma(c) chain than CD4(+) T cells, which may explain the improvement of CD8(+) T-cell growth in the presence of IL-2 + IL-7 + IL-15. Immunohistochemical identification of IL-15 and the higher mRNA expression of IL-15R alpha, IL-7 and gamma(c) chain in CCC heart tissues compared with control individuals indicate in situ production of survival cytokines and their receptors in CCC hearts. Together, our results suggest that local production of IL-7 and IL-15 may be associated with the maintenance and predominance of CD8(+) T cells, the cells effecting tissue damage in CCC hearts.
Asunto(s)
Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/patología , Cardiomiopatía Chagásica/inmunología , Cardiomiopatía Chagásica/patología , Interleucina-15/biosíntesis , Interleucina-7/biosíntesis , Miocardio/inmunología , Miocardio/patología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD4-Positivos/patología , Linfocitos T CD8-positivos/metabolismo , Línea Celular , Movimiento Celular/inmunología , Proliferación Celular , Supervivencia Celular/inmunología , Cardiomiopatía Chagásica/metabolismo , Enfermedad Crónica , Humanos , Inmunofenotipificación , Interleucina-15/fisiología , Interleucina-2/biosíntesis , Interleucina-2/fisiología , Interleucina-7/fisiología , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/metabolismo , Leucocitos Mononucleares/patología , Recuento de Linfocitos , Miocardio/metabolismoRESUMEN
Bone marrow culture and molecular cloning techniques have permitted rapid progress to be made in identifying molecules that stimulate or inhibit particular steps in blood cell formation. Two types of factors that influence B lymphocyte precursors are considered in this brief review. Cell adhesion molecules are probably needed to correctly position immature precursors within the marrow and some of the most important of these have been identified. Recent studies suggest that local or systemically derived hormones must also be added to the list of agents which can markedly influence the production of lymphocytes.