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The rationale for the IL‐2‐independent generation of the self‐renewing central memory CD8 + T cells
Author(s) -
Fearon Douglas T.,
Carr James M.,
Telaranta Aino,
Carrasco Marlene J.,
Thaventhiran James E. D.
Publication year - 2006
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/j.0105-2896.2006.00390.x
Subject(s) - biology , effector , cytotoxic t cell , microbiology and biotechnology , cd8 , population , il 2 receptor , immunology , stem cell , memory t cell , t cell , antigen , immune system , genetics , in vitro , medicine , environmental health
Summary: Clones of CD8 + T cells that have been selected in the primary response must have a mechanism by which they can continuously or intermittently generate new effector cells. Several years ago, this mechanism was proposed to involve a self‐renewing, stem cell‐like subset that could avoid the differentiating effects of interleukin‐2 (IL‐2). The model considered the stem cell subset to be contained within the central memory population of CD8 + T cells (T CM ). This proposal was inconsistent with subsequent findings suggesting that all antigen‐activated CD8 + T cells differentiated to effector cells (T EFF ) during the primary response and that T CM developed during the memory phase by de‐differentiating from effector memory cells (T EM ). However, findings have since been reported that support the stem cell model. First, studies indicate that T EM do not serve as the precursors of T CM . Second, transcriptional repressors of IL‐2 signaling do enhance the memory response. Third, memory cells lacking effector functions and with a capacity to replicate in a secondary response develop in the absence of signaling through the IL‐2/IL‐15 receptor. Taken together, these findings suggest that antigen‐activated CD8 + T cells with a stem cell‐like capability for maintaining proliferative potential develop by an unknown IL‐2‐independent process. The challenge is now to identify this unknown pathway of clonal expansion.