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Title: | CD43 signals induce type one lineage commitment of human CD4(+) T cells |
Authors: | Ramirez-Pliego, O Escobar-Zarate, DL Rivera-Martínez, GM Cervantes-Badillo, MG Esquivel-Guadarrama, FR Rosas-Salgado, G Rosenstein, Y Santana, MA |
Issue Date: | 2007 |
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 IFN gamma in human T cells. In freshly isolated CD4(+) T cells, CD43 signals potentiated expression of the IFN gamma gene induced by TcR activation this was not seen in CD8(+) T cells. In effector cells, CD43 signals alone induced the expression of the IFN gamma 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 TI lineage. In support of this, CD43 signals induced a transient membrane expression of the high-affinity chains of the receptors for IL-12 and IFN gamma in CD4(+) T cells. CD43 and TcR signals also cooperated with those of IL-12 in the induction of IFN gamma expression. Moreover, CD43 signals induced the co-clustering of IFN gamma R 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 TI commitment. Conclusion: Our results suggest a key role for CD43 signals in the differentiation of human CD4(+) T cells into a TI pattern. |
URI: | http://hdl.handle.net/11154/1049 |
ISSN: | 1471-2172 |
Appears in Collections: | Ciencias
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