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

• Main Authors: Rosenstein Yvonne, Rosas-Salgado Gabriela, Esquivel-Guadarrama Fernando R, Cervantes-Badillo Mayte G, Rivera-Martínez Gemma M, Escobar-Zárate Diana L, Ramírez-Pliego Oscar, Santana M Angélica
• Format: Article
• Language: English
• Published: BMC 2007-11-01
• Series: BMC Immunology
• Online Access: http://www.biomedcentral.com/1471-2172/8/30

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>CD43 signals direct the expression of IFNγ in human T cells. In freshly isolated CD4⁺T cells, CD43 signals potentiated expression of the IFNγ gene induced by TcR activation; this was not seen in CD8⁺T cells. In effector cells, CD43 signals alone induced the expression of the IFNγ 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 IFNγ in CD4⁺T cells. CD43 and TcR signals also cooperated with those of IL-12 in the induction of IFNγ expression. Moreover, CD43 signals induced the co-clustering of IFNγR 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.</p> <p>Conclusion</p> <p>Our results suggest a key role for CD43 signals in the differentiation of human CD4⁺T cells into a T1 pattern.</p>