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Publication : CD4+ T cells support cytotoxic T lymphocyte priming by controlling lymph node input.

First Author  Kumamoto Y Year  2011
Journal  Proc Natl Acad Sci U S A Volume  108
Issue  21 Pages  8749-54
PubMed ID  21555577 Mgi Jnum  J:171892
Mgi Id  MGI:5002374 Doi  10.1073/pnas.1100567108
Citation  Kumamoto Y, et al. (2011) CD4+ T cells support cytotoxic T lymphocyte priming by controlling lymph node input. Proc Natl Acad Sci U S A 108(21):8749-54
abstractText  Rapid induction of CD8(+) cytotoxic T lymphocyte (CTL) responses is critical to combat acute infection with intracellular pathogens. CD4(+) T cells help prime antigen-specific CTLs in secondary lymphoid organs after infection in the periphery. Although the frequency of naive precursors is very low, the immune system is able to efficiently screen for cognate CTLs through mechanisms that are not well understood. Here we examine the role of CD4(+) T cells in early phases of the immune response. We show that CD4(+) T cells help optimal CTL expansion by facilitating entry of naive polyclonal CD8(+) T cells into the draining lymph node (dLN) early after infection or immunization. CD4(+) T cells also facilitate input of naive B cells into reactive LNs. Such 'help' involves expansion of the arteriole feeding the dLN and enlargement of the dLN through activation of dendritic cells. In an antigen- and CD40-dependent manner, CD4(+) T cells activate dendritic cells to support naive lymphocyte recruitment to the dLN. Our results reveal a previously unappreciated mode of CD4(+) T-cell help, whereby they increase the input of naive lymphocytes to the relevant LN for efficient screening of cognate CD8(+) T cells.
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