Four Functionally Distinct Populations of Human Effector-Memory CD8 super(+) T Lymphocytes

• Published in: Journal of Immunology 2007-04, Vol.178 (7), p.4112-4119
• Main Authors: Romero, Pedro, Zippelius, Alfred, Kurth, Isabel, Pittet, Mikaeel J, Touvrey, Cedric, Iancu, Emanuela M, Corthesy, Patricia, Devevre, Estelle, Speiser, Daniel E, Rufer, Nathalie
• Format: Article
• Language: English
• ISSN: 0022-1767; 1365-2567

In humans, the pathways of memory and effector T cell differentiation remain poorly defined. We have dissected the functional properties of ex vivo effector-memory (EM) CD45RA super(-)CCR7 super(-) T lymphocytes present within the circulating CD8 super(+) T cell pool of healthy individuals. Our studies show that EM T cells are heterogeneous and are subdivided based on differential CD27 and CD28 expression into four subsets. EM sub(1) (CD27 super(+)CD28 super(+)) and EM sub(4) (CD27 super(-)CD28 super(+)) T cells express low levels of effector mediators such as granzyme B and perforin and high levels of CD127/IL-7R alpha . EM sub(1) cells also have a relatively short replicative history and display strong ex vivo telomerase activity. Therefore, these cells are closely related to central-memory (CD45RA super(-)CCR7 super(+)) cells. In contrast, EM sub(2) (CD27 super(+)CD28 super(-)) and EM sub(3) (CD27 super(-)CD28 super(-)) cells express mediators characteristic of effector cells, whereby EM sub(3) cells display stronger ex vivo cytolytic activity and have experienced larger numbers of cell divisions, thus resembling differentiated effector (CD45RA super(+)CCR7 super(-)) cells. These data indicate that progressive up-regulation of cytolytic activity and stepwise loss of CCR7, CD28, and CD27 both characterize CD8 super(+) T cell differentiation. Finally, memory CD8 super(+) T cells not only include central-memory cells but also EM sub(1) cells, which differ in CCR7 expression and may therefore confer memory functions in lymphoid and peripheral tissues, respectively.