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© The Rockefeller University Press, 0022-1007/2000/2/541/ $5.00
The Journal of Experimental Medicine, Volume 191, Number 3, February 7, 2000 541-550

Original Article

Cd40-Independent Pathways of T Cell Help for Priming of Cd8+ Cytotoxic T Lymphocytes

Zhengbin Lua, Lingxian Yuana, Xianzheng Zhoua, Eduardo Sotomayora, Hyam I. Levitskya, and Drew M. Pardolla

a Johns Hopkins University School of Medicine Oncology Center, Baltimore, Maryland 21231
Johns Hopkins University School of Medicine Oncology Center, 1650 Orleans St., Bunting-Blaustein Suite 444, Baltimore, MD 21231.410-614-0549410-955-7866

dmpardol{at}jhmi.edu

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.

Key Words: cross-priming • dendritic cells • CD40 • CD4+ help • CD8+ cytotoxic T lymphocytes

Abbreviations used in this paper: DC, dendritic cell; ELISPOT, enzyme-linked immunospot; HA, hemagglutinin; NP, nuclear protein; Tg, transgenic; vac, vaccinia virus.

E. Sotomayor's current address is H. Lee Moffit Cancer Center and Research Institute, University of South Florida, Tampa, FL 33612.

© 2000 The Rockefeller University Press


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