A Role for Toll-Like Receptor 4 in Dendritic Cell Activation and Cytolytic CD8+ T Cell Differentiation in Response to a Recombinant Heat Shock Fusion Protein

Deborah Palliser, Qian Huang, Nir Hacohen, Steven P. Lamontagne, Eduardo Guillen, Richard A. Young, Herman N. Eisen

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Recombinant heat shock fusion proteins (Hsfp) injected into mice without added adjuvants can stimulate production of CD8 cytolytic T cells. Because initiation of productive immune responses generally requires dendritic cell (DC) activation, the question arises as to whether the Hsfp can activate DC independently of contaminating LPS. Using microarray analyses of DC from LPS-insensitive mice having a point mutation in Toll-like receptor 4 (Tlr4) (C3H/HeJ), lacking Tlr4 (B10/ScNCr), we show here that unlike a LPS standard, Hsfp activated DC from HeJ mice almost as well as DC from wild-type mice. Consistent with the microarray analysis, the Hsfp's ability to activate DC was not eliminated by polymyxin B but was destroyed by proteinase K. The Hsfp did not, however, stimulate DC from mice lacking Tlr4. In vivo the CD8 T cell response to the Hsfp in mice lacking Tlr4 was impaired: the responding CD8 cells initially proliferated vigorously but their development into cytolytic effector cells was diminished. Overall, the results indicate that this Hsfp can activate DC independently of LPS but still requires Tlr4 for an optimal CD8 T cell response.

Original languageEnglish (US)
Pages (from-to)2885-2893
Number of pages9
JournalJournal of Immunology
Volume172
Issue number5
DOIs
Publication statusPublished - Mar 1 2004

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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