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


CONCLUSIONS
Our results suggest a key role for CD43 signals in the differentiation of human CD4+ T cells into a T1 pattern.
Facultad de Ciencias, Universidad Autónoma del Estado de Morelos, Av, Universidad 1001, Col, Chamilpa, Cuernavaca, 62210, Mexico. raplos2002@yahoo.com.mx
Oscar
O
Ramírez-Pliego
Diana L
DL
Escobar-Zárate
Gemma M
GM
Rivera-Martínez
Mayte G
MG
Cervantes-Badillo
Fernando R
FR
Esquivel-Guadarrama
Gabriela
G
Rosas-Salgado
Yvonne
Y
Rosenstein
M Angélica
MA
Santana
D000328:Adult; D000911:Antibodies, Monoclonal; D002450:Cell Communication / Q000276:immunology; D019070:Cell Lineage / Q000276:immunology*; D002478:Cells, Cultured; D005434:Flow Cytometry; D050990:GATA3 Transcription Factor / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D051917:Leukosialin / Q000276:immunology* / Q000378:metabolism*; D008213:Lymphocyte Activation; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D053707:Receptors, Interleukin-12 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D015533:Transcriptional Activation / Q000276:immunology
D000911:Antibodies, Monoclonal; D050990:GATA3 Transcription Factor; D051917:Leukosialin; D011948:Receptors, Antigen, T-Cell; D053707:Receptors, Interleukin-12; D007371:Interferon-gamma