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Publication : CD40-independent pathways of T cell help for priming of CD8(+) cytotoxic T lymphocytes.

First Author  Lu Z Year  2000
Journal  J Exp Med Volume  191
Issue  3 Pages  541-50
PubMed ID  10662799 Mgi Jnum  J:115118
Mgi Id  MGI:3690688 Doi  10.1084/jem.191.3.541
Citation  Lu Z, et al. (2000) CD40-independent pathways of T cell help for priming of CD8(+) cytotoxic T lymphocytes. J Exp Med 191(3):541-50
abstractText  In many cases, induction of CD8(+) CTL responses requires CD4(+) T cell help. Recently, it has been shown that a dominant pathway of CD4(+) help is via antigen-presenting cell (APC) activation through engagement of CD40 by CD40 ligand on CD4(+) T cells. To further study this three cell interaction, we established an in vitro system using dendritic cells (DCs) as APCs and influenza hemagglutinin (HA) class I and II peptide-specific T cell antigen receptor transgenic T cells as cytotoxic T lymphocyte precursors and CD4(+) T helper cells, respectively. We found that CD4(+) T cells can provide potent help for DCs to activate CD8(+) T cells when antigen is provided in the form of either cell lysate, recombinant protein, or synthetic peptides. Surprisingly, this help is completely independent of CD40. Moreover, CD40-independent CD4(+) help can be documented in vivo. Finally, we show that CD40-independent T cell help is delivered through both sensitization of DCs and direct CD4(+)-CD8(+) T cell communication via lymphokines. Therefore, we conclude that CD4(+) help comprises at least three components: CD40-dependent DC sensitization, CD40-independent DC sensitization, and direct lymphokine-dependent CD4(+)-CD8(+) T cell communication.
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