Wortmannin, a phosphatidylinositol 3-kinase inhibitor, blocks antigen-mediated, but not CD3 monoclonal antibody-induced, activation of murine CD4+ T cells.
J Immunol
; 158(10): 4688-95, 1997 May 15.
Article
in En
| MEDLINE
| ID: mdl-9144481
ABSTRACT
Perturbation of several distinct T cell molecules, including the CD3/TCR complex, CD7, and CD28, activates phosphatidylinositol 3-kinase (PI3-K), but a clear consensus on the role of PI3-K in T cell activation has yet to emerge. We report here that CD3 mAb-induced IL-2 production by CD4+ T cells from DO11.10 TCR-alphabeta-transgenic mice is refractory to the potent PI3-K inhibitor, wortmannin, demonstrating that activation under these conditions is independent of PI3-K. In marked contrast, wortmannin substantially inhibits IL-2 production elicited by Ag (OVA(323-339) peptide) presented by appropriate APCs (syngeneic B7+ B cell blasts) and blocks Ag-induced differentiation of naive CD4+ DO11.10 T cells into IL-4-producing cells. Wortmannin inhibits Ag-induced conjugate formation between T cells and B7+ B cell blasts. Because T cell activation by Ag requires stable interactions with APCs, this inhibitory effect on conjugate formation may underlie the ability of wortmannin to block Ag-induced IL-2 production and differentiation.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Lymphocyte Activation
/
Receptors, Antigen, T-Cell
/
CD4-Positive T-Lymphocytes
/
CD3 Complex
/
Phosphotransferases (Alcohol Group Acceptor)
/
Enzyme Inhibitors
/
Androstadienes
Limits:
Animals
Language:
En
Journal:
J Immunol
Year:
1997
Document type:
Article
Affiliation country: