PMID- 11748273
OWN - NLM
STAT- MEDLINE
DCOM- 20020114
LR  - 20210105
IS  - 0022-1007 (Print)
IS  - 1540-9538 (Electronic)
IS  - 0022-1007 (Linking)
VI  - 194
IP  - 12
DP  - 2001 Dec 17
TI  - Cytokine-driven proliferation and differentiation of human naive, central memory, 
      and effector memory CD4(+) T cells.
PG  - 1711-9
AB  - Memory T lymphocytes proliferate in vivo in the absence of antigen maintaining a 
      pool of central memory T cells (T(CM)) and effector memory T 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, that 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 failed to respond. Dendritic cells (DCs) and 
      DC-derived cytokines allowed naive T cells to proliferate selectively in response 
      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 
      (gamma(c)). The extracellular signal regulated kinase and the p38 
      mitogen-activated protein (MAP) kinases were selectively required for TCR and 
      cytokine-driven proliferation, respectively. Importantly, in cytokine-driven 
      cultures, some of the proliferating T(CM) differentiated to T(EM)-like cells 
      acquiring effector function and switching chemokine receptor expression from CCR7 
      to CCR5. The sustained antigen-independent generation of T(EM) from a pool of 
      T(CM) cells provides a plausible mechanism for the maintenance of a polyclonal 
      and functionally diverse repertoire of human CD4(+) memory T cells.
FAU - Geginat, J
AU  - Geginat J
AD  - Institute for Research in Biomedicine, Bellinzona 6500, Switzerland. 
      jens.geginat@irb.unisi.ch
FAU - Sallusto, F
AU  - Sallusto F
FAU - Lanzavecchia, A
AU  - Lanzavecchia A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Exp Med
JT  - The Journal of experimental medicine
JID - 2985109R
RN  - 0 (Cytokines)
SB  - IM
MH  - CD4-Positive T-Lymphocytes/cytology/*immunology
MH  - Cell Differentiation/drug effects/*immunology
MH  - Cell Division/drug effects/immunology
MH  - Cytokines/*immunology/pharmacology
MH  - Humans
MH  - Immunologic Memory
MH  - T-Lymphocyte Subsets/cytology/*immunology
PMC - PMC2193568
EDAT- 2001/12/19 10:00
MHDA- 2002/01/15 10:01
PMCR- 2002/06/17
CRDT- 2001/12/19 10:00
PHST- 2001/12/19 10:00 [pubmed]
PHST- 2002/01/15 10:01 [medline]
PHST- 2001/12/19 10:00 [entrez]
PHST- 2002/06/17 00:00 [pmc-release]
AID - 011514 [pii]
AID - 10.1084/jem.194.12.1711 [doi]
PST - ppublish
SO  - J Exp Med. 2001 Dec 17;194(12):1711-9. doi: 10.1084/jem.194.12.1711.