INTRACELLULAR EXPRESSION OF MICA IN ACTIVATED CD4 T LYMPHOCYTES AND PROTECTION FROM NK CELL-MEDIATED MICA-DEPENDENT CYTOTOXICITY

CAROLINA INÉS DOMAICA; LUCIANA LORENA MOLINERO; MERCEDES BEATRIZ FUERTES; MARÍA VICTORIA GIRART; NORBERTO WALTER ZWIRNER

Córdoba, Argentina

Congreso; VII Congreso Latinoamericano de Inmunología.; 2005

Asociación Latinoamericana de Inmunología

            MICA is a stress-regulated molecule recognized by the NK cell activating receptor NKG2D. Previously, we demonstrated that MICA is induced on T cells stimulated with mitogenic cytokines. However, the biological consequences of MICA expression in T lymphocytes remain unexplored. Here, we show by western blot that in vitro differentiated Th1 and Th2 cells also up-regulated MICA expression, but surface expression was not detected. Isolated CD4+ T lymphocytes stimulated with PMA and ionomycin, also induced MICA expression as assessed by western blot, but only low levels were expressed at the cell surface. Activated but not resting CD4+ T lymphocytes were lysed by IL-15- or IL-2-stimulated NK cells, but susceptibility was increased when HLA class I molecules were blocked. Also, cytokine-stimulated NK cells produced more IFN-g when cultured with activated CD4+ T lymphocytes. However, blocking experiments did not show a participation of MICA in these responses. Confocal microscopy revealed that MICA is mostly retained inside activated CD4+ T cells. Our results suggest that intracellular retention and low surface expression of MICA on activated CD4+ T lymphocytes might be a safeguard mechanism that protects them from NK cells in an inflammatory microenvironment, where NK and activated CD4+ T cells are recruited.