CD40-independent pathways of T cell help for priming of CD8(+) cytotoxic T lymphocytes.
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.
Lu
Z
Z
Johns Hopkins University School of Medicine Oncology Center, Baltimore, Maryland 21231, USA.
Yuan
L
L
Zhou
X
X
Sotomayor
E
E
Levitsky
H I
HI
Pardoll
D M
DM
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002450:Cell Communication / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D015398:Signal Transduction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000945:Antigens, Differentiation, T-Lymphocyte; D008222:Lymphokines