Activated T cells express the OX40 ligand: requirements for induction and costimulatory function

I Mendel, EM Shevach - Immunology, 2006 - Wiley Online Library
I Mendel, EM Shevach
Immunology, 2006Wiley Online Library
Summary OX40/OX40 ligand (OX40L) interactions have been shown to exert potent
costimulatory effects on T‐cell activation. OX40 expression is transiently up‐regulated on T
cells following T‐cell receptor engagement, while OX40L is expressed on antigen‐
presenting cells following activation. Although expression of the OX40L by T cells has been
reported, the requirements for induction of OX40L on T cells have not been studied in detail.
Here, we demonstrate that the OX40L can be induced on murine CD4+ and CD8+ T cells …
Summary
OX40/OX40 ligand (OX40L) interactions have been shown to exert potent costimulatory effects on T‐cell activation. OX40 expression is transiently up‐regulated on T cells following T‐cell receptor engagement, while OX40L is expressed on antigen‐presenting cells following activation. Although expression of the OX40L by T cells has been reported, the requirements for induction of OX40L on T cells have not been studied in detail. Here, we demonstrate that the OX40L can be induced on murine CD4+ and CD8+ T cells after 6 days of culture under T helper type 1 (Th1) conditions, but not under Th2 conditions. Induction of OX40L expression required a high concentration of interleukin‐12 (IL‐12), was not seen in the presence of interferon‐γ, and was dependent on signal transducer and activator of transcription type 4 (STAT4). Notably, induction of OX40L on T cells was only seen at very low concentrations of antigen or anti‐CD3. T‐cell‐expressed OX40L was fully capable of delivering a potent costimulatory signal that enhanced the proliferation of CD4+ T cells as well as promoted their differentiation to Th2 cells. OX40L expression could also be induced on CD4+ T cells in vivo following immunization with low‐dose antigen and an IL‐12 inducer. OX40/OX40L interactions between antigen‐specific T cells may occur in T‐cell zones in lymph node and spleen when OX40L expression has diminished on APC. Costimulation by T‐cell‐expressed OX40L may result in deviation of a Th1 response to a Th2 response under conditions where T cells are exposed to low concentrations of foreign or autoantigens in the presence of high concentrations of IL‐12.
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