Memory T lymphocytes divide in vivo in the absence of antigen maintaining a pool of central memory (T-CM) and effector memory cells (T-EM) with distinct effector function and homing capacity. We compared human CD4(+) naive T, T-CM and T-EM cells for their capacity to proliferate in response to cytokines. which have been implicated in T cell homeostasis. Interleukin (IL)-7 and IL-15 expanded with very high efficiency T-EM, while T-CM were less responsive and naive T cells did not respond at all. Dendritic cell (DC)-derived cytokines allowed naive T cells to respond selectively to IL-4 and potently boosted the response of T-CM to IL-7 and IL-15 by increasing the expression of the IL-2/IL-15Rbeta and the common gamma chain (gammac). The ERK and the p38 MAP kinases were selectively required for TCR and cytokine-driven proliferation, respectively. Importantly, in cytokine-driven cultures T-CM proliferated and some of the proliferating cells acquired effector function and non-lymphoid tissue homing capacity. Ex vivo BrdU incorporation experiments showed that both T-CM and Term, proliferated under steady state conditions in vivo. Altogether these results provide a plausible mechanism for the maintenance of a polyclonal and functionally diverse repertoire of human CD4(+) memory T cells and for a sustained antigen-independent generation of T-EM froth a pool of T-CM cells.
Cytokine-driven proliferation and differentiation of human naive, central memory and effector memory CD4(+) T cells / J. Geginat, F. Sallusto, A. Lanzavecchia. - In: PATHOLOGIE BIOLOGIE. - ISSN 0369-8114. - 51:2(2003), pp. 64-66. ((Intervento presentato al 6. convegno Symposium on Dendritic Cells tenutosi a Brisbane nel 2001.
|Titolo:||Cytokine-driven proliferation and differentiation of human naive, central memory and effector memory CD4(+) T cells|
|Parole Chiave:||naive CD4(+) T lymphocytes; central memory; effector memory; cytokines; dendritic cells|
|Settore Scientifico Disciplinare:||Settore MED/04 - Patologia Generale|
|Data di pubblicazione:||2003|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/S0369-8114(03)00098-1|
|Appare nelle tipologie:||01 - Articolo su periodico|