CD43 signals induce type one lineage commitment of human CD4+ T cells
Por:
Ramírez-Pliego O., Escobar-Zárate D.L., Rivera-Martínez G.M., Cervantes-Badillo M.G., Esquivel-Guadarrama F.R., Rosas-Salgado G., Rosenstein Y., Santana M.A.
Publicada:
1 ene 2007
Categoría:
Immunology
Resumen:
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?in human T cells. In freshly isolated CD4+ T cells, CD43 signals potentiated expression of the IFN? 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? 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 IFN? in CD4+ T cells. CD43 and TcR signals also cooperated with those of IL-12 in the induction of IFN? expression. Moreover, CD43 signals induced the co-clustering of IFN?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 T1 commitment. Conclusion: Our results suggest a key role for CD43 signals in the differentiation of human CD4+ T cells into a T1 pattern. © 2007 Ramírez-Pliego et al; licensee BioMed Central Ltd.
Filiaciones:
Ramírez-Pliego O.:
Facultad de Ciencias, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001, Col. Chamilpa, Cuernavaca 62210, Mexico
Escobar-Zárate D.L.:
Facultad de Ciencias, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001, Col. Chamilpa, Cuernavaca 62210, Mexico
Rivera-Martínez G.M.:
Facultad de Ciencias, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001, Col. Chamilpa, Cuernavaca 62210, Mexico
Cervantes-Badillo M.G.:
Facultad de Ciencias, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001, Col. Chamilpa, Cuernavaca 62210, Mexico
Esquivel-Guadarrama F.R.:
Facultad de Medicina, Universidad Autónoma del Estado Morelos, Av. Universidad 1001, Col. Chamilpa, Cuernavaca 62210, Mexico
Rosas-Salgado G.:
Facultad de Medicina, Universidad Autónoma del Estado Morelos, Av. Universidad 1001, Col. Chamilpa, Cuernavaca 62210, Mexico
Rosenstein Y.:
Instituto de Biotecnología, Universidad Nacional Autónoma de México, Av. Universidad 2001, Col. Cuernavaca 62210, Mexico
Santana M.A.:
Facultad de Ciencias, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001, Col. Chamilpa, Cuernavaca 62210, Mexico
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