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Selected Toll-like Receptor Ligands and Viruses Promote Helper-Independent Cytotoxic T Cell Priming by Upregulating CD40L on Dendritic Cells

2009; Cell Press; Volume: 30; Issue: 2 Linguagem: Inglês

10.1016/j.immuni.2008.11.015

1097-4180

Susan Johnson, Yifan Zhan, Robyn M. Sutherland, Adele M. Mount, Sammy Bedoui, Jamie L. Brady, Emma M. Carrington, Lorena E. Brown, Gabrielle T. Belz, William R. Heath, Andrew M. Lew,

T-cell and B-cell Immunology

CD40L (CD154) on CD4+ T cells has been shown to license dendritic cells (DCs) via CD40 to prime cytotoxic T lymphocyte (CTL) responses. We found that the converse (CD40L on DCs) was also important. Anti-CD40L treatment decreased endogenous CTL responses to both ovalbumin and influenza infection even in the absence of CD4+ T cells. DCs expressed CD40L upon stimulation with agonists to Toll-like receptor 3 (TLR3) and TLR9. Moreover, influenza infection, which stimulates CTLs without help, upregulated CD40L on DCs, but herpes simplex infection, which elicits CTLs through help, did not. CD40L-deficient (Cd40lg−/−) DCs are suboptimal both in vivo in bone marrow chimera experiments and in vitro in mixed lymphocyte reactions. In contrast, Cd40lg−/− CD8+ T cells killed as effectively as wild-type cells. Thus, CD40L upregulation on DCs promoted optimal priming of CD8+ T cells without CD4+ T cells, providing a mechanism by which pathogens may elicit helper-independent CTL immunity.