Prevalence of CD8(+)alpha beta T cells in Trypanosoma cruzi-elicited myocarditis is associated with acquisition of CD62L(Low)LFA-1(High)VLA-4(High) activation phenotype and expression of IFN-gamma-inducible adhesion and chemoattractant molecules.
The determinants of the prevalence of CD8(+) T cells in the inflamed myocardium of Trypanosoma cruzi-infected patients and experimental animals are undefined. Using C3H/He mice infected with the Colombiana strain of T. cruzi, we found that the distribution of CD4(+)/CD8(-) and CD4(-)/CD8(+) T cells in the myocardium mirrors the frequency of cells expressing the CD62L(Low)LFA-1(High)VLA-4(High) activation phenotype among CD4(+)/CD8(-) and CD4(-)/CD8(+ )peripheral blood T cells. Consistently, vascular cell adhesion molecule-1-positive endothelial cells and a fine fibronectin network surrounding VLA-4(+) mononuclear cells were found in the inflamed myocardium. Further, interferon gamma (IFN-gamma) and IFN-gamma-induced chemokines (RANTES, MIG and CRG-2/IP-10), as well as JE/MCP-1 and MIP1-alpha, were found to be the dominant cytokines expressed in situ during acute and chronic myocarditis elicited by T. cruzi. In contrast, interleukin 4 mRNA was only detected during the chronic phase. Altogether, the results indicate that the distribution of T-cell subsets in the myocardium of T. cruzi-infected mice reflects the particular profile of adhesion molecules acquired by most peripheral CD8(+) T lymphocytes and point to the possibility that multiple IFN-gamma-inducible molecules present in the inflamed tissue contribute to the establishment and maintenance of T. cruzi-induced myocarditis.
dos Santos
P V
PV
Laboratory of Autoimmunity and Immunoregulation, Department of Immunology, IOC-Fiocruz, Av. Brasil 4365, 21045-900, Rio de Janeiro, RJ, Brazil.
Roffê
E
E
Santiago
H C
HC
Torres
R A
RA
Marino
A P
AP
Paiva
C N
CN
Silva
A A
AA
Gazzinelli
R T
RT
Lannes-Vieira
J
J
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D002598:Chagas Cardiomyopathy / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D018925:Chemokines / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D016130:Immunophenotyping; D039041:Integrin alpha4beta1; D016023:Integrins / Q000032:analysis*; D007371:Interferon-gamma / Q000494:pharmacology*; D019041:L-Selectin / Q000032:analysis*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000032:analysis*; D051379:Mice; D008809:Mice, Inbred C3H; D009206:Myocardium / Q000473:pathology; D018512:Parasitemia / Q000401:mortality; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis*; D016201:Receptors, Lymphocyte Homing / Q000032:analysis*
D015815:Cell Adhesion Molecules; D018925:Chemokines; D016207:Cytokines; D039041:Integrin alpha4beta1; D016023:Integrins; D016169:Lymphocyte Function-Associated Antigen-1; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016201:Receptors, Lymphocyte Homing; D019041:L-Selectin; D007371:Interferon-gamma