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[Phenotype and reactivity of T-lymphocytes isolated from atheromatous plaque. Knowledge obtained from a transplant
T Ramírez1, E Rodríguez, V Ruiz
1Departamento de Biología Celular, Instituto Nacional de Cardiología Ignacio Chávez INCICH, México, D.F.
The primary immunologic hypothesis assumes that the initial damage in atherosclerotic lesions is mediated by T lymphocytes reactive to heat shock proteins, lipoproteins, bacteria, virus or even donor MHC antigens. A frequent cause of heart transplant failure is the de novo formation of atheromatous lesions in the vessels of the transplanted organ despite their absence in the donor, thus suggesting that new lesions are secondary to a cellular immune response by the receptor. In this study we determined the phenotype and the reactivity of T cells from peripheral blood and from endomyocardial and atherectomy biopsies obtained from the same immunosuppressed patient who underwent a heart transplant in 1989. A panel of homozygous HLA-typed, Epstein-Barr virus transformed B lymphocytes were used as stimulators in functional assays. Our results showed an important increase in the percentage of CD4+ cells in the atheromatous plaque as well as in the endomyocardium, and a considerable amount of TCR sigma+ lymphocytes in the atheromatous plaque. A considerable loss of alloreactivity to HLA antigens was also observed. These results suggest that although there are adequate conditions to mount a cellular immune response a state of cellular anergy exists towards HLA antigens probably as result of prolonged immunosuppressive therapy. The presence of obstructive lesions in this particular patient don't seem to be secondary to HLA alloreactivity but could be secondary to a switch in the cellular immune response as a consequence of chronic exposure to some donor antigen, thus explaining the increased proportion of TCR sigma+T lymphocytes.
The primary immunologic hypothesis assumes that the initial damage in atherosclerotic lesions is mediated by T lymphocytes reactive to heat shock proteins, lipoproteins, bacteria, virus or even donor MHC antigens. A frequent cause of heart transplant failure is the de novo formation of atheromatous lesions in the vessels of the transplanted organ despite their absence in the donor, thus suggesting that new lesions are secondary to a cellular immune response by the receptor. In this study we determined the phenotype and the reactivity of T cells from peripheral blood and from endomyocardial and atherectomy biopsies obtained from the same immunosuppressed patient who underwent a heart transplant in 1989. A panel of homozygous HLA-typed, Epstein-Barr virus transformed B lymphocytes were used as stimulators in functional assays. Our results showed an important increase in the percentage of CD4+ cells in the atheromatous plaque as well as in the endomyocardium, and a considerable amount of TCR sigma+ lymphocytes in the atheromatous plaque. A considerable loss of alloreactivity to HLA antigens was also observed. These results suggest that although there are adequate conditions to mount a cellular immune response a state of cellular anergy exists towards HLA antigens probably as result of prolonged immunosuppressive therapy. The presence of obstructive lesions in this particular patient don't seem to be secondary to HLA alloreactivity but could be secondary to a switch in the cellular immune response as a consequence of chronic exposure to some donor antigen, thus explaining the increased proportion of TCR sigma+T lymphocytes.