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

Abstract

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. EM1 (CD27+CD28+) and EM4 (CD27−CD28+) T cells express low levels of effector mediators such as granzyme B and perforin and high levels of CD127/IL-7Rα. EM1 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, EM2 (CD27+CD28−) and EM3 (CD27−CD28−) cells express mediators characteristic of effector cells, whereby EM3 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 EM1 cells, which differ in CCR7 expression and may therefore confer memory functions in lymphoid and peripheral tissues, respectively.

The IL-7Rα Pathway Is Quantitatively and Functionally Altered in CD8 T Cells in Multiple Sclerosis

“…Natalizumab (Tysabri), a blocking monoclonal blocking Ab against VLA-4 is an approved treatment for MS (38). Moreover, CD8EM T cells have the capacity to migrate to nonlymphoid tissues (39). In the case of MS, they potentially migrate into the CNS, where they re-encounter IL-7 (Fig.…”

Immune profiling of Alzheimer patients

“…We therefore compared T cell differentiation status in AD patients versus old controls, using multiple markers including the CD27 and CD28 costimulatory molecules, which are crucial for T cell activation. It has been reported that expression of these two markers is reduced proportional to the degree of differentiation of the T cell (Romero et al, 2007). Naïve cells are CD28 + CD27+ while the latest stage of T cell differentiation is accompanied by the loss of both CD28 and CD27 (Koch et al, 2008).…”

Sialyl lewisx antigen-expressing human CD4+ T and CD8+ T cells as initial immune responders in memory phenotype subsets

“…Memory phenotype T cells are further divided into subpopulations according to the combination of these expression levels [13][14][15]. Many studies have revealed that the memory phenotype human T cells existed in the peripheral tissues, depending on the expression levels of adhesion molecules and chemokine receptors [1,2].…”