Locally produced survival cytokines IL-15 and IL-7 may be associated to the predominance of CD8+ T cells at heart lesions of human chronic Chagas disease cardiomyopathy.
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.
Fonseca
S G
SG
Laboratory of Immunology, Heart Institute of the Sao Paulo University Medical School, Sao Paulo, Brazil.
Reis
M M
MM
Coelho
V
V
Nogueira
L G
LG
Monteiro
S M
SM
Mairena
E C
EC
Bacal
F
F
Bocchi
E
E
Guilherme
L
L
Zheng
X X
XX
Liew
F Y
FY
Higuchi
M L
ML
Kalil
J
J
Cunha-Neto
E
E
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D002460:Cell Line; D002465:Cell Movement / Q000276:immunology; D049109:Cell Proliferation; D002470:Cell Survival / Q000276:immunology; D002598:Chagas Cardiomyopathy / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D002908:Chronic Disease; D006801:Humans; D016130:Immunophenotyping; D019409:Interleukin-15 / Q000096:biosynthesis* / Q000502:physiology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000502:physiology; D015851:Interleukin-7 / Q000096:biosynthesis* / Q000502:physiology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018655:Lymphocyte Count; D009206:Myocardium / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*
C508605:IL7 protein, human; D019409:Interleukin-15; D007376:Interleukin-2; D015851:Interleukin-7