1: Nat Immunol. 2003 Feb;4(2):182-8. Epub 2003 Jan 13. 

CTLA-4 regulates the requirement for cytokine-induced signals in T(H)2 lineage
commitment.

Bour-Jordan H, Grogan JL, Tang Q, Auger JA, Locksley RM, Bluestone JA.

UCSF Diabetes Center and Department of Medicine, University of California San
Francisco, 94143, USA.

The relative importance of the cytokine milieu versus cytolytic T
lymphocyte-associated antigen 4 (CTLA-4) and T cell receptor signal strength on
T cell differentiation remains unclear. Here we have generated mice deficient
for signal transducer and activator of transcription 6 (STAT6) and CTLA-4 to
determine the role of CTLA-4 in cytokine-driven T cell differentiation.
CTLA-4-deficient T cells bypass the need for STAT6 in the differentiation of T
helper type 2 (T(H)2) cells. T(H)2 differentiation of cells deficient for both
STAT6 and CTLA-4 is accompanied by induction of GATA-3 and the migration of
T(H)2 cells to peripheral tissues. CTLA-4 deficiency also affects the balance of
the nuclear factors NFATc1 and NFATc2, and enhances activation of NF-kappaB.
These results suggest that CTLA-4 has a critical role in T cell differentiation
and that STAT6-dependent T(H)2 lineage commitment and stabilization can be
bypassed by increasing the strength of signaling through the T cell receptor.

PMID: 12524538 [PubMed - indexed for MEDLINE]


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