Four Functionally Distinct Populations of Human Effector-Memory CD8+ T Lymphocytes.
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(-)CCR7(-) T lymphocytes present within the circulating CD8(+) 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(1) (CD27(+)CD28(+)) and EM(4) (CD27(-)CD28(+)) T cells express low levels of effector mediators such as granzyme B and perforin and high levels of CD127/IL-7Ralpha. EM(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(-)CCR7(+)) cells. In contrast, EM(2) (CD27(+)CD28(-)) and EM(3) (CD27(-)CD28(-)) cells express mediators characteristic of effector cells, whereby EM(3) cells display stronger ex vivo cytolytic activity and have experienced larger numbers of cell divisions, thus resembling differentiated effector (CD45RA(+)CCR7(-)) cells. These data indicate that progressive up-regulation of cytolytic activity and stepwise loss of CCR7, CD28, and CD27 both characterize CD8(+) T cell differentiation. Finally, memory CD8(+) T cells not only include central-memory cells but also EM(1) cells, which differ in CCR7 expression and may therefore confer memory functions in lymphoid and peripheral tissues, respectively.[1]References
- Four Functionally Distinct Populations of Human Effector-Memory CD8+ T Lymphocytes. Romero, P., Zippelius, A., Kurth, I., Pittet, M.J., Touvrey, C., Iancu, E.M., Corthesy, P., Devevre, E., Speiser, D.E., Rufer, N. J. Immunol. (2007) [Pubmed]
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