Another Twist in the Extrathymic Tale

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Science  16 May 2008:
Vol. 320, Issue 5878, pp. 851
DOI: 10.1126/science.320.5878.851c

αβ T cells are descended from progenitors within the thymus, yet additional sites of lymphogenesis may also exist, most notably the mucosa of the gut. A decade ago, compelling evidence for intestinal extrathymic αβ T cell development appeared with the report of small gut lymphoid aggregates called cryptopatches (CPs) that contained progenitors able to repopulate the T cell compartments of a mouse. Then, a few years ago, controversy was ignited by an elaborate fate-mapping study that concluded that all intestinal αβ T cells are thymus-derived after all. In that study, the transcription factor retinoic acid-related orphan receptor γt (RORγt) was required for both gut and thymic T cell development, but this could be uncoupled from CP development and function. Thus, it was concluded that CPs are not genuine sites of lymphocyte development, but rather are lymphoid aggregates, induced by lymphoid tissue-inducing (LTi) cells and required for intestinal immune responses.

Naito et al. have performed further detailed analyses of the same engineered mouse strains used in the second study and find that CPs harbor a more complex mix of cells than was originally apparent, of which only a minority are actually LTi-like. Indeed, many CP cells with absent or minimal RORγt expression displayed the telltale signs of differentiating T cells, even in animals that did not possess a thymus. The case for extrathymic αβ T cell development may now be re-reinforced, but we still remain some way from understanding the function of these unusual T cells. — SJS

Mucosal Immunol. 1, 198 (2008).

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