Counting antigen-specific CD8 T cells: a reevaluation of bystander activation during viral infection.
Viral infections induce extensive T cell proliferation in vivo, but the specificity of the majority of the responding T cells has not been defined. To address this issue we used tetramers of MHC class I molecules containing viral peptides to directly visualize antigen-specific CD8 T cells during acute LCMV infection of mice. Based on tetramer binding and two sensitive assays measuring interferon-gamma production at the single-cell level, we found that 50%-70% of the activated CD8 T cells were LCMV specific [2 x 10(7) virus-specific cells/spleen]. Following viral clearance, antigen-specific CD8 T cell numbers dropped to 10(6) per spleen and were maintained at this level for the life of the mouse. Upon rechallenge with LCMV, there was rapid expansion of memory T cells, but after infection with the heterologous vaccinia virus there was no detectable change in the numbers of LCMV-specific memory CTL. Therefore, much of the CD8 T cell expansion seen during viral infection represents antigen-specific cells and warrants a revision of our current thinking on the size of the antiviral response.
Murali-Krishna
K
K
Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Altman
J D
JD
Suresh
M
M
Sourdive
D J
DJ
Zajac
A J
AJ
Miller
J D
JD
Slansky
J
J
Ahmed
R
R
D000818:Animals; D017951:Antigen Presentation; D000956:Antigens, Viral / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D007110:Immunity, Active; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D018655:Lymphocyte Count / Q000379:methods*; D008216:Lymphocytic Choriomeningitis / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology
D000956:Antigens, Viral; D015395:Histocompatibility Antigens Class I; D010446:Peptide Fragments; D007371:Interferon-gamma