T cell diversity

Patrick writes: "Virginal CD8 T cells encountering MHC-associated antigen will undergo activation, proliferation, gaining effector functions, followed by contraction and the development of central and effector T cell memories. A number of models have been proposed to account for the generation of these T cell subsets. The observation of homeostatic proliferation suggests that virginal CD8 T cells may not have been as naïve as one have previously thought. This proliferation may have given rise to intraclonal diversity and pre-programmed the “naïve” precursors to develop into differing subsets when encountering antigens. An alternative “progressive differentiation” model proposes that different signal strength at the time of priming may give rise to the diverse subsets. An extension of this model is that a stronger signal may impact the differentiation pattern of one naïve T cells encountering antigen on a DC in contrast to two or three naïve T cells encountering the antigen on the same DC. A “latecomer effect”, i.e., a naïve T cell encountering the antigen late, also may drive the development of long-living T cells.

In this report (Immunity. 2007 Dec 21;27(6):985-997), Stemberger et al. developed a single cell adoptive transfer system to show one CD8+ CD45+ naïve T cell can give rise to diverse phenotypic subsets with functionality (as measured by degranulation, IL-2, IFNg and TNFα expression), including T effectors (CD127-lo, CD62L-lo); effector memory T cells (CD127-hi, CD62L-lo); and, central memory T cells (CD127-hi, CD62L-hi). The observed phenotypic and functional patterns of these subsets are comparable to those seen in resident CD8+ CD45+ T cells upon antigen activation. This in vivo assay, while technically challenging, may provide a handle to study the factors that promote the differentiation and development of effector and central memories."
Stemberger et al. Immunity. 2007 Dec 21;27(6):985-997. A Single Naive CD8(+) T Cell Precursor Can Develop into Diverse Effector and Memory Subsets.