Functional subsets within clonally expanded CD8(+) memory T cells in elderly humans.
With advancing age, healthy humans frequently demonstrate large clonal expansions of CD8(+) T cells in the peripheral blood, which persist for long periods of time and appear to be maintained as a population of memory cells. We studied nine large T cell clones in five elderly individuals. We noted that in most cases the expanded clones were dominated by cells that did not express CD28, a pivotal molecule in T cell activation, and these clones proliferated poorly in culture. However, nearly all of the clonal expansions had CD28(+) fractions and some of these cells appeared to lose CD28 gene expression with stimulation in culture. CD28(+) cells demonstrated greater proliferation in both bulk and limiting dilution cultures compared to CD28(-) cells bearing the same TCR, whereas CD28(-) cells showed increased perforin expression. Together, these data suggest that loss of CD28 expression marks functional differentiation to cytotoxic memory cells within these clonal expansions and likely within CD8(+) memory populations in general.
Chamberlain
W D
WD
Department of Medicine and Department of Immunology, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
Falta
M T
MT
Kotzin
B L
BL
D000368:Aged / Q000502:physiology*; D018106:CD28 Antigens / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D002999:Clone Cells / Q000473:pathology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D007156:Immunologic Memory; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D018106:CD28 Antigens; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin