CD40-independent pathways of T cell help for priming of CD8+ cytotoxic T lymphocytes

Zhengbin Lu, Lingxian Yuan, Xianzheng Zhou, Eduardo Sotomayor, Hyam I. Levitsky, Andrew Mark Pardoll

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)541-550
Number of pages10
JournalJournal of Experimental Medicine
Volume191
Issue number3
DOIs
StatePublished - Feb 7 2000

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Cytotoxic T-Lymphocytes
T-Lymphocytes
Dendritic Cells
Cell Communication
Lymphokines
Peptide T
CD40 Ligand
Antigen-Presenting Cells
Helper-Inducer T-Lymphocytes
T-Cell Antigen Receptor
Recombinant Proteins
Human Influenza
Antigens
Peptides

Keywords

  • CD40
  • CD4 help
  • CD8 cytotoxic T lymphocytes
  • Cross-priming
  • Dendritic cells

ASJC Scopus subject areas

  • Immunology

Cite this

CD40-independent pathways of T cell help for priming of CD8+ cytotoxic T lymphocytes. / Lu, Zhengbin; Yuan, Lingxian; Zhou, Xianzheng; Sotomayor, Eduardo; Levitsky, Hyam I.; Pardoll, Andrew Mark.

In: Journal of Experimental Medicine, Vol. 191, No. 3, 07.02.2000, p. 541-550.

Research output: Contribution to journalArticle

Lu, Zhengbin ; Yuan, Lingxian ; Zhou, Xianzheng ; Sotomayor, Eduardo ; Levitsky, Hyam I. ; Pardoll, Andrew Mark. / CD40-independent pathways of T cell help for priming of CD8+ cytotoxic T lymphocytes. In: Journal of Experimental Medicine. 2000 ; Vol. 191, No. 3. pp. 541-550.
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