Cyclosporine-resistant, Rab27a-independent mobilization of intracellular preformed CD40L mediates antigen-specific T cell help in vitro (63.8)
| Autor: | Jennifer Gardell, Timothy Thauland, David Parker, Yoshinobu Koguchi |
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| Rok vydání: | 2011 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 186:63.8-63.8 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.186.supp.63.8 |
| Popis: | CD40L is critically important for the initiation and maintenance of adaptive immune responses. CD40L expression in CD4+ T cells is regulated transcriptionally and produced from new mRNA following antigen recognition. However, recent studies with two-photon microscopy revealed that most cognate interactions between effector CD4+ T cells and APCs are too short for de novo synthesis of CD40L. Given that effector and memory CD4+ T cells store preformed CD40L (pCD40L) in a secretory compartment that comes to the cell surface within minutes of antigenic stimulation, we and others have proposed that pCD40L might mediate T cell-dependent activation of cognate APCs during these brief encounters. However, it has not been shown that the relatively small amount of pCD40L is sufficient to activate APCs, owing to the difficulty of separating the effects of pCD40L from those of de novo CD40L and other cytokines in vitro. Here we show that pCD40L surface mobilization is resistant to cyclosporine or FK506 treatment, while this treatment fully inhibits de novo cytokine expression. This allows us to dissect the role of pCD40L in APC activation. We find that pCD40L mediates selective activation of cognate but not bystander APCs in vitro and pCD40L mobilization does not depend on Rab27a, which is required for mobilization of lytic granules. Therefore, effector CD4+ T cells deliver pCD40L specifically to APCs on the same time scale as the lethal hit of CTLs but with distinct molecular machinery. |
| Databáze: | OpenAIRE |
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