International Immunology, Vol. 11, No. 2, 229-241,
February 1999
© 1999 Japanese Society for Immunology
Differentiation of human CD8 T cells: implications for in vivo persistence of CD8+CD28– cytotoxic effector clones
Immunology Program, Graduate School of Medical Sciences, and the Department of Medicine, Cornell University, Weill Medical College, 1300 York Avenue, Box 56, New York, NY 10021
Correspondence to: D. N. Posnett
CD8 T cells contain a distinct subset of CD8+CD28– cells. These cells are not present at birth and their frequency increases with age. They frequently contain expanded clones using various TCR
ß receptors and these clones can represent >50% of all CD8 cells, specially in old subjects or patients with chronic viral infections such as HIV-1. Herein, it is shown that a large fraction of CD8+CD28– cells expresses intracellular perforin by three-color flow cytometry, in particular when this subset is expanded. Together with their known ability to exert potent re-directed cytotoxicity, this indicates that CD8+CD28– T cells comprise cytotoxic effector cells. With BrdU labeling, we show that CD8+CD28– cells derive from CD8+CD28+ precursors in vitro. In addition, sorted CD8+CD28+ cells gave rise to a population of CD8+CD28– cells after allo-stimulation. Moreover, ex vivo CD8+CD28+ cells contain the majority of CD8 blasts, supporting the notion that they contain the proliferative precursors of CD8+CD28– cells. CD95 (Fas) expression was lower in CD8+CD28– cells, and this subset was less prone to spontaneous apoptosis in ex vivo samples and more resistant to activation-induced cell death induced by a superantigen in vitro. Thus, the persistence of expanded clones in vivo in the CD8+CD28– subset may be explained by antigen-driven differentiation from CD8+CD28+ memory precursors, with relative resistance to apoptosis as the clones become perforin+ effector cells.
Keywords: age, apoptosis, CD8, CD28, human, oligoclonal, TCR
Transmitting editor: A. Singer
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