Commitment point during G0-->G1 that controls entry into the cell cycle.

Abstract:

:Initiation of T-lymphocyte-mediated immune responses involves two cellular processes: entry into the cell cycle (G(0)-->G(1)) for clonal proliferation and coordinated changes in surface and secreted molecules that mediate effector functions. However, a point during G(0)-->G(1) beyond which T cells are committed to enter the cell cycle has not been defined. We define here a G(0)-->G(1) commitment point that occurs 3 to 5 h after CD3 and CD28 stimulation of human CD4 or CD8 T cells. Transition through this point requires cdk6/4-cyclin D, since inhibition with TAT-p16(INK4A) during the first 3 to 5 h prevents cell cycle entry and maintains both naive and memory T cells in G(0). Transition through the G(0)-->G(1) commitment point is also necessary for T cells to increase in size, i.e., to enter the cellular growth cycle. However, transition through this point is not required for the induction of effector functions. These can be initiated while cells are maintained in G(0) with TAT-p16(INK4A). We have termed this quiescent, activated state G(0(A)). Our data provide proof of the principle that entry of T cells into the cell cycle and cellular growth cycles are coupled at the G(0)-->G(1) commitment point but that these processes can be uncoupled from the early expression of molecules of effector functions.

journal_name

Mol Cell Biol

authors

Lea NC,Orr SJ,Stoeber K,Williams GH,Lam EW,Ibrahim MA,Mufti GJ,Thomas NS

doi

10.1128/mcb.23.7.2351-2361.2003

subject

Has Abstract

pub_date

2003-04-01 00:00:00

pages

2351-61

issue

7

eissn

0270-7306

issn

1098-5549

journal_volume

23

pub_type

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