Multiple survival signals are delivered by dendritic cells to naive CD4+ T cells.
The molecular mechanisms by which dendritic cells (DC) favor naive T cell survival in mice have been examined in co-cultures of DC and naive CD4+ T cells. Naive T cells can survive in the presence of IL-4 or IL-7, but DC-induced T cell survival requires direct cell-cell interactions and does not seem to be mediated by these or other soluble factors. Classical MHC II molecules on DC are not necessary for T cell survival as long as hybrid AalphaEbeta MHC class II molecules are present. In the total absence of MHC II molecules on DC, T cell survival is reduced by half, and CD3zeta phosphorylation fully disappears. These results contrast with the classical view that naive T cell survival is associated with CD3zeta phosphorylation and depends mostly on IL-7 and MHC-TCR interactions. We demonstrate that DC-induced T cell survival is a multi-factorial process that also involves CD28, LFA-1 and another (as yet undefined) surface molecule that requires the activity of src (but not phosphatidylinositol-3-) kinase.
Feuillet
Vincent
V
Département de Biologie Cellulaire, Institut Cochin, Paris, France.
Lucas
Bruno
B
Di Santo
James P
JP
Bismuth
Georges
G
Trautmann
Alain
A
D000818:Animals; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology*; D002470:Cell Survival / Q000276:immunology; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology*; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D015151:Immunoblotting; D015847:Interleukin-4 / Q000276:immunology; D015851:Interleukin-7 / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010766:Phosphorylation; D019061:src-Family Kinases / Q000276:immunology
D018106:CD28 Antigens; D017252:CD3 Complex; C121704:CD3 antigen, zeta chain; D000949:Histocompatibility Antigens Class II; D015851:Interleukin-7; D016169:Lymphocyte Function-Associated Antigen-1; D015847:Interleukin-4; D019061:src-Family Kinases