Intracellular expression of MICA in activated CD4 T lymphocytes and protection from NK cell-mediated MICA-dependent cytotoxicity.

CAROLINA INES DOMAICA; LUCIANA LORENA MOLINERO; MERCEDES BEATRIZ FUERTES; MARÍA VICTORIA GIRART; LUCAS EZEQUIEL ROSSI; NORBERTO WALTER ZWIRNER

HUMAN IMMUNOLOGY

Elsevier

Lugar: New York; Año: 2006 vol. 67 p. 170 - 182

0198-8859

MICA is a stress-regulated molecule recognized by the NK cell activating receptor NKG2D. Previously, we demonstrated that MICA is induced on activated T cells but regulation by mitogenic cytokines and its biological consequences remain unexplored. Here, we show that IL-2, IL-4 and IL-15 but not TNF-alfa, induced MICA expression in T lymphocytes present in PBMCs, as assessed by western blot. IL-2 effect involved Jak3/STAT5, p38 MAPK, p70 kinase, Lck/fyn kinases, and NF-kB. MICA expression was also observed in Th1 and Th2 cells. However, surface expression was not detected. T lymphocytes present in PBMCs and 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 poorly lysed by IL-15- or IL-2-stimulated NK cells, but susceptibility was acquired when HLA class I molecules were blocked. Also, cytokine-stimulated NK cells produced more IFN-gamma after culture with activated CD4+ T lymphocytes. However, we could not demonstrate the participation of MICA in these responses. Confocal microscopy revealed that MICA is mostly retained inside activated CD4+ T cells. Our results suggest that low surface expression of MICA on activated CD4+ T lymphocytes might be a safeguard mechanism to protect them from NK cells in an inflammatory, virus-infected or tumor microenvironment, where NK and activated CD4+ T cells are recruited.