IL-2 and IL-15 regulate CD154 expression on activated CD4 T cells.
The cellular and humoral immune system is critically dependent upon CD40-CD154 (CD40 ligand) interactions between CD40 expressed on B cells, macrophages, and dendritic cells, and CD154 expressed primarily on CD4 T cells. Previous studies have shown that CD154 is transiently expressed on CD4 T cells after T cell receptor engagement in vitro. However, we found that stimulation of PBLs with maximal CD28 costimulation, using beads coupled to Abs against CD3 and CD28, led to a very prolonged expression of CD154 on CD4 cells (>4 days) that was dependent upon autocrine IL-2 production. Previously activated CD4 T cells could respond to IL-2, or the related cytokine IL-15, by de novo CD154 production and expression without requiring an additional signal from CD3 and CD28. These results provide evidence that CD28 costimulation of CD4 T cells, through autocrine IL-2 production, maintains high levels of CD154 expression. This has significant impact on our understanding of the acquired immune response and may provide insight concerning the mechanisms underlying several immunological diseases.
Skov
S
S
Xcyte Therapies, Seattle, WA 98104, USA. s.skov@immi.ku.dk
Bonyhadi
M
M
Odum
N
N
Ledbetter
J A
JA
D000938:Antigen-Presenting Cells / Q000276:immunology; D018106:CD28 Antigens / Q000502:physiology; D017252:CD3 Complex / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D019013:CD40 Antigens / Q000378:metabolism; D023201:CD40 Ligand; D019703:Calcineurin / Q000502:physiology; D002450:Cell Communication / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D006801:Humans; D019409:Interleukin-15 / Q000502:physiology*; D007376:Interleukin-2 / Q000502:physiology*; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000502:physiology; D013997:Time Factors; D014407:Tumor Cells, Cultured
D018106:CD28 Antigens; D017252:CD3 Complex; D019013:CD40 Antigens; D019409:Interleukin-15; D007376:Interleukin-2; D008024:Ligands; D008562:Membrane Glycoproteins; D023201:CD40 Ligand; D019703:Calcineurin