Two subsets of memory T lymphocytes with distinct homing potentials and effector functions

Abstract

Naive T lymphocytes travel to T-cell areas of secondary lymphoid organs in search of antigen presented by dendritic cells. Once activated, they proliferate vigorously, generating effector cells that can migrate to B-cell areas or to inflamed tissues. A fraction of primed T lymphocytes persists as circulating memory cells that can confer protection and give, upon secondary challenge, a qualitatively different and quantitatively enhanced response. The nature of the cells that mediate the different facets of immunological memory remains unresolved. Here we show that expression of CCR7, a chemokine receptor that controls homing to secondary lymphoid organs, divides human memory T cells into two functionally distinct subsets. CCR7- memory cells express receptors for migration to inflamed tissues and display immediate effector function. In contrast, CCR7+ memory cells express lymph-node homing receptors and lack immediate effector function, but efficiently stimulate dendritic cells and differentiate into CCR7- effector cells upon secondary stimulation. The CCR7+ and CCR7- T cells, which we have named central memory (TCM) and effector memory (TEM), differentiate in a step-wise fashion from naive T cells, persist for years after immunization and allow a division of labour in the memory response.

Ex vivo AKT-inhibition facilitates generation of polyfunctional stem cell memory-like CD8+ T cells for adoptive immunotherapy

“…19 Normally, terminally differentiated CD8 + T cells show diminished secretion of IL-2. 47 As our Akt-inhibited T cell products effeciently co-produced IL-2 and IFN-γ, this reflects the superior polyfunctionality of our T cells.…”

Immunological memories of the bone marrow

“…In mice, memory T cells have been classified according to low expression of CD45RB,69, 70 and stable acquisition of high CD44 expression 71. Taking a closer look at the functional potential of circulating antigen‐experienced T lymphocytes, Sallusto and Lanzavecchia classified them as “central” memory cells, expressing the chemokine receptor CCR7, and “effector” memory cells not expressing CCR7 72. CCR7 is involved in the organization of immune reactions in secondary lymphoid organs 73.…”

The roles of resident, central and effector memory CD4 T‐cells in protective immunity following infection or vaccination

“…Instead they, like naïve T‐cells, express high levels of CD62L, which enables entry into lymph nodes from the blood via high endothelial venules and CCR7, the chemokine receptor that is also involved in trafficking to and within lymphoid organs 45, 56…”