T cell diversity: E Unum Pluribus

Infections stimulate the expansion of a few individual progenitor T lymphocytes, perhaps as few as 50, into millions of specific T lymphocytes (Review). These T cell clones are typically diverse, encompassing subsets of short-lived effector cells, long-lived memory cells, and a variety of intermediate subsets. The proposed models of diversification focus on the priming phase because previous observations have shown that an initial, transient encounter with antigen suffices to induce protracted proliferation and complete subset diversity. Differentiation capabilities might be predetermined, with the naive precursor cells programmed to undergo diversification into all subsets. Alternatively, a ‘‘progressive differentiation’’ model proposes that the strength of antigen stimulation and costimulation at priming determines how far the T cell progeny are driven along a differentiation spectrum.

Here, the ability of precursor T cells to differentiate into multiple subsets was tested by transferring a single naive T cell and then analyzing its progeny after immunization. Twelve days after transfer and immunization of the host with intracellular bacteria expressing ovalbumin, (L.m.-ova), the donor (CD45.1+) transgenic, ova-specific T cells were found to generate many subsets of CD8+ T cells, including CD127+ memory T cells detected in spleen and lymph nodes. The figure, derived from fig. 1A, shows 2 host mice, one on each row; progeny of the transferred cell, the CD45.1+ population circled in the left panels, could be detected in about a quarter of the host mice. Progeny T cells were also detected in lungs. Both 'effector' and 'central' memory T cells (low vs. high CD62L) were detected, the former in the lymphoid organs and latter in the lungs. Upon restimulation of the progeny in vitro, production of the inflammatory cytokines interferon-gamma and tumor-necrosis-factor was detected, demonstrating maturation into effector T cells. This is a straightforward test, albeit technically demanding, that provides strong evidence that a single naïve T cell can generate many, and perhaps all, subsets.
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.