Optimal induction of antigen-specific CD8+ T cell responses requires bystander cell participation.
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.
Brice
Gary T
GT
Malaria Program, Naval Medical Research Center, Silver Spring, Maryland 20910, USA.
Graber
Norma L
NL
Carucci
Daniel J
DJ
Doolan
Denise L
DL
D000328:Adult; D000956:Antigens, Viral / Q000276:immunology*; D024201:Bystander Effect / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000096:biosynthesis; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology; D008875:Middle Aged
D000956:Antigens, Viral; C080810:CXCL9 protein, human; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma