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Rac1‐mediated Bcl‐2 induction is critical in antigen‐induced CD4 single‐positive differentiation of a CD4 + CD8 + immature thymocyte line
Author(s) -
Oda Hiroyo,
Suzuki Harumi,
Sakai Kouhei,
Kitahara Seiji,
Patrick Michael S.,
Azuma Yoshinao,
Sugi Kazuro,
Kitamura Toshio,
Kaye Jonathan,
Shirai Mutsunori
Publication year - 2007
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.1005585
Subject(s) - biology , t cell receptor , rac1 , thymocyte , microbiology and biotechnology , cd8 , apoptosis , signal transduction , cellular differentiation , t cell , antigen , immunology , immune system , biochemistry , gene
Rac1, one of the Rho family small guanosine triphosphatases, has been shown to work as a “molecular switch” in various signal transduction pathways. To assess the function of Rac1 in the differentiation process of CD4 single‐positive (CD4‐SP) T cells from CD4CD8 double‐positive (DP) cells, we used a DP cell line DPK, which can differentiate into CD4‐SP cells upon TCR stimulation in vitro. DPK expressing dominant‐negative (dn)Rac1 underwent massive apoptosis upon TCR stimulation and resulted in defective differentiation of CD4‐SP cells. Conversely, overexpression of dnRac2 did not affect differentiation. TCR‐dependent actin polymerization was inhibited, whereas early ERK activation was unaltered in dnRac1‐expressing DPK. We found that TCR‐dependent induction of Bcl‐2 was suppressed greatly in dnRac1‐expressing DPK, and this suppression was independent of actin rearrangement. Furthermore, introduction of exogenous Bcl‐2 inhibited TCR‐dependent induction of apoptosis and restored CD4‐SP generation in dnRac1‐expressing DPK without restoring TCR‐induced actin polymerization. Collectively, these data indicate that Rac1 is critical in differentiation of CD4‐SP from the DP cell line by preventing TCR‐induced apoptosis via Bcl‐2 up‐regulation.