TY - JOUR
T1 - CD40-independent pathways of T cell help for priming of CD8+ cytotoxic T lymphocytes
AU - Lu, Zhengbin
AU - Yuan, Lingxian
AU - Zhou, Xianzheng
AU - Sotomayor, Eduardo
AU - Levitsky, Hyam I.
AU - Pardoll, Drew M.
PY - 2000/2/7
Y1 - 2000/2/7
N2 - 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.
AB - 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.
KW - CD4 help
KW - CD40
KW - CD8 cytotoxic T lymphocytes
KW - Cross-priming
KW - Dendritic cells
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U2 - 10.1084/jem.191.3.541
DO - 10.1084/jem.191.3.541
M3 - Article
C2 - 10662799
AN - SCOPUS:0034614891
SN - 0022-1007
VL - 191
SP - 541
EP - 550
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 3
ER -