Journal of Leukocyte Biology eBioscience full spectrum cell analysis
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(Journal of Leukocyte Biology. 2002;72:1164-1171.)
© 2002 by Society for Leukocyte Biology

Optimal induction of antigen-specific CD8+ T cell responses requires bystander cell participation

Gary T. Brice*, Norma L. Graber*,{dagger}, Daniel J. Carucci* and Denise L. Doolan*,{ddagger}

* Malaria Program, Naval Medical Research Center, Silver Spring, Maryland;
{dagger} Henry M. Jackson Foundation, Rockville, Maryland; and
{ddagger} Department of Molecular Microbiology and Immunology, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, Maryland

Correspondence: Dr. Denise L. Doolan, Malaria Program, Naval Medical Research Center, 503 Robert Grant Avenue, Lab 3W16, Silver Spring, MD 20910. E-mail: dooland{at}nmrc.navy.mil

Efficient activation of specific immune responses requires a concerted interaction between T cells and antigen-presenting cells. A requirement for bystander participation of CD4+ T cells for expansion and maintenance of memory CD8+ T cells has been noted in several models, but a role with regard to effector CD8+ T responses has not been well-defined. In this report, the requirement of bystander participation for optimal induction of antigen-specific CD8+ T cell effector function was determined by directly quantitating antigen-specific interferon-{gamma} (IFN-{gamma}) CD8+ T cell responses by enzyme-linked immunospot assays, and by indirectly evaluating induction of the chemokine monokine induced by IFN-{gamma} as a marker for IFN-{gamma}-mediated effector function. Our results demonstrate that bystander cell participation, mediated by CD4+ T cell and natural killer (NK) cells, is required for optimal induction of antigen-specific CD8+ T cell effector responses. Our data further establish a novel role for NK cells in the activation of antigen-specific immune responses.

Key Words: chemokines • cytokines • FACS • T lymphocytes • bystander activation




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