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BMC Immunol. 2007 Nov 23;8:30.

CD43 signals induce Type One lineage commitment of human CD4+ T cells.

Author information

1
Facultad de Ciencias, Universidad Autónoma del Estado de Morelos, Av, Universidad 1001, Col, Chamilpa, Cuernavaca, 62210, Mexico. raplos2002@yahoo.com.mx

Abstract

BACKGROUND:

The activation and effector phenotype of T cells depend on the strength of the interaction of the TcR with its cognate antigen and additional signals provided by cytokines and by co-receptors. Lymphocytes sense both the presence of an antigen and also clues from antigen-presenting cells, which dictate the requisite response. CD43 is one of the most abundant molecules on the surface of T cells; it mediates its own signalling events and cooperates with those mediated by the T cell receptor in T cell priming. We have examined the role of CD43 signals on the effector phenotype of adult CD4+ and CD8+ human T cells, both alone and in the presence of signals from the TcR.

RESULTS:

CD43 signals direct the expression of IFNgamma in human T cells. In freshly isolated CD4+ T cells, CD43 signals potentiated expression of the IFNgamma gene induced by TcR activation; this was not seen in CD8+ T cells. In effector cells, CD43 signals alone induced the expression of the IFNgamma gene in CD4+ T cells and to a lesser extent in CD8+ cells. The combined signals from CD43 and the TcR increased the transcription of the T-bet gene in CD4+ T cells and inhibited the transcription of the GATA-3 gene in both populations of T cells, thus predisposing CD4+ T cells to commitment to the T1 lineage. In support of this, CD43 signals induced a transient membrane expression of the high-affinity chains of the receptors for IL-12 and IFNgamma in CD4+ T cells. CD43 and TcR signals also cooperated with those of IL-12 in the induction of IFNgamma expression. Moreover, CD43 signals induced the co-clustering of IFNgammaR and the TcR and cooperated with TcR and IL-12 signals, triggering a co-capping of both receptors in CD4+ populations, a phenomenon that has been associated with a T1 commitment.

CONCLUSION:

Our results suggest a key role for CD43 signals in the differentiation of human CD4+ T cells into a T1 pattern.

PMID:
18036228
PMCID:
PMC2235884
DOI:
10.1186/1471-2172-8-30
[Indexed for MEDLINE]
Free PMC Article

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