Lower GrB+ CD62Lhigh CD8 TCM effector lymphocyte response to influenza virus in older adults is associated with increased CD28null CD8 T lymphocytes.
Older adults who are at risk of developing influenza illness, have a low level of influenza virus-stimulated cytotoxic T lymphocyte (CTL) activity as measured by an assay of granzyme B (GrB). The purpose of this study was to determine whether aging affected memory CTL populations identified by GrB expression in influenza virus-stimulated peripheral blood mononuclear cells (PBMC). The expression and activity of GrB increased with virus stimulation over 5 days of culture. Virus-specific CD8 effector T cells with the phenotype, GrB+ CD62L(high) CD8 T(CM), were found to be the source of the early CTL response to influenza virus. Comparing the CD8 T cell response in 5-day PBMC cultures of 161 adult subjects, the response of GrB+ CD62L(high) CD8 T(CM) lymphocytes in older individuals was significantly lower than in younger adults after viral stimulation (p<0.001). The increase in the proportion of CD28(null) CD8 T cells in fresh PBMC negatively correlated with the proportion GrB+ CD62L(high) CD8 T(CM) lymphocytes in virus-stimulated PBMC. Thus, the increase in CD28(null) CD8 T cells with age may contribute to the limited CTL response to influenza vaccination and diminished protection in older adults.
Xie
Dongxu
D
Center for Immunotherapy of Cancer and Infectious Diseases, MC 1601, Department of Immunology, University of Connecticut School of Medicine, 263 Farmington Avenue, Farmington, CT 06030-1601, USA.
McElhaney
Janet E
JE
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000276:immunology*; D018106:CD28 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D005260:Female; D053804:Granzymes / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D007156:Immunologic Memory; D007252:Influenza Vaccines / Q000276:immunology*; D019041:L-Selectin / Q000032:analysis; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D009975:Orthomyxoviridae / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D018106:CD28 Antigens; D016827:CD8 Antigens; D007252:Influenza Vaccines; D019041:L-Selectin; D053804:Granzymes