Cytotoxic T lymphocyte antigen 4 is induced in the thymus upon in vivo activation and its blockade prevents anti-CD3-mediated depletion of thymocytes.

CM Cilio, MR Daws, A Malashicheva, CL Sentman, D. Holmberg

Результат исследований: Научные публикации в периодических изданияхстатья

45 Цитирования (Scopus)

Аннотация

The development of a normal T cell repertoire in the thymus is dependent on the interplay between signals mediating cell survival (positive selection) and cell death (negative selection or death by neglect). Although the CD28 costimulatory molecule has been implicated in this process, it has been difficult to establish a role for the other major costimulatory molecule, cytotoxic T lymphocyte antigen (CTLA)-4. Here we report that in vivo stimulation through the T cell receptor (TCR)-CD3 complex induces expression of CTLA-4 in thymocytes and leads to the association of CTLA-4 with the SH2 domain-containing phosphatase (SHP)-2 tyrosine phosphatase. Moreover, intrathymic CTLA-4 blockade dramatically inhibits anti-CD3-mediated depletion of CD4+CD8+ double positive immature thymocytes. Similarly, anti-CD3-mediated depletion of CD4+CD8+ double positive cells in fetal thymic organ cultures could also be inhibited by anti-CTLA-4 antibodies. Thus, our data provide evidence for a role of CTLA-4 in thymic selection and s
Язык оригиналаанглийский
Страницы (с-по)1239-1246
ЖурналJournal of Experimental Medicine
Том188
Номер выпуска7
DOI
СостояниеОпубликовано - 1998
Опубликовано для внешнего пользованияДа

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