Activation-induced expression of MICA on T lymphocytes involves engagement of CD3 and CD28.
MICA is an HLA-related cell stress-regulated antigen recognized by cytotoxic cells expressing the NKG2D molecule. Although resting lymphocytes do not express MICA, it can be induced on PHA-activated T cells. Here, we demonstrate by Western blot that MICA is induced on allogeneic-activated CD4(+) and CD8(+) T lymphocytes. Blocking activation with anti-HLA class I, anti-HLA-DR, or anti-CD86 mAb affected the expression of MICA slightly. When T cells were stimulated with anti-CD3 or anti-CD28 mAb plus PMA, a sustained up-regulation of MICA was observed by Western blot, RT-PCR, and flow cytometry. The expression of MICA reached a plateau at day 4 after CD3 engagement and at day 3 after anti-CD28/PMA stimulation. Conversely, the proliferative response reached a peak at day 4. Hence, CD3 or CD28 engagement induces MICA expression on T lymphocytes. This activation-induced expression might participate in NKG2D-mediated cytotoxicity toward activated T cells to maintain homeostasis during an ongoing immune response.
Molinero
Luciana L
LL
Laboratorio de Inmunogenética, Hospital de Clínicas José de San Martín, Facultad de Medicina, Universidad de Buenos Aires, Av. Cordoba 2351, 3er piso, 1120 Buenos Aires, Argentina.
Fuertes
Mercedes B
MB
Rabinovich
Gabriel A
GA
Fainboim
Leonardo
L
Zwirner
Norberto W
NW
D000911:Antibodies, Monoclonal / Q000276:immunology; D018106:CD28 Antigens / Q000276:immunology / Q000378:metabolism*; D017252:CD3 Complex / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007519:Isoantigens / Q000276:immunology; D007700:Kinetics; D008213:Lymphocyte Activation; D012333:RNA, Messenger / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000276:immunology*; D015533:Transcriptional Activation
D000911:Antibodies, Monoclonal; D018106:CD28 Antigens; D017252:CD3 Complex; D015395:Histocompatibility Antigens Class I; D007519:Isoantigens; C099187:MHC class I-related chain A; D012333:RNA, Messenger