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Anatomical Heterogeneity of Memory CD4⁺ T Cells Due to Reversible Adaptation to the Microenvironment¹

Division of Molecular Immunology, National Institute for Medical Research, London, United Kingdom

The memory T cell pool is characterized by a substantial degree of heterogeneity in phenotype and function as well as anatomical distribution, but the underlying mechanisms remain unclear. In this study we confirm that the memory CD4⁺ T cell pool in wild-type and TCR-transgenic mice consists of heterogeneous subsets, as defined by surface marker expression or cytokine production. Extralymphoid sites contain significant numbers of memory CD4⁺ T cells, which are phenotypically and functionally distinct from their lymphoid counterparts. However, we show in this study that the phenotype of lymphoid and extralymphoid memory T cells is not stable. Instead, the unique properties of extralymphoid memory T cells are acquired upon migration into extralymphoid sites and are lost when memory T cells migrate back into lymphoid organs. Thus, at least some of the extralymphoid properties may represent a transient activation state that can be adopted by T cells belonging to a single memory T cell pool. Furthermore, such intermittent activation during or after migration into extralymphoid sites could provide an important signal, promoting the survival and functional competence of memory T cells in the absence of Ag.

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