Two Niches in the Bone Marrow: A Hypothesis on Life-long T Cell Memory

The concept is emerging that the bone marrow (BM) sustains life-long persistence of memory T cells, as it does for plasma cells. Recent studies revived the debate on how this is achieved: is the BM essentially a nest for the proliferation of recirculating memory T cells, or a storage depot for resting memory T cells? Learning from division of labor in hematopoietic stem cells, this article proposes that two distinct BM niches support memory T cell cycling and quiescence, thereby enabling memory T cells to maintain all their distinguishing features. This framework might be instrumental to interpret some puzzling findings and conceptualize the mechanisms preserving either stability of memory T cell numbers or the capacity to mount secondary responses.

TrendsNaive T cells expand and differentiate into effector and memory T cells upon priming. After antigen clearance, most of the antigen-specific T cells die and the few cells that survive generate a long-lived pool of memory T cells.Memory T cells persist for years or even decades (memory phase) and rapidly divide and assume effector function upon re-exposure to antigen (secondary response).Recirculating and tissue-resident memory T cells work in conjunction to provide both systemic and local immunity.Several studies have highlighted that memory T cell lodging into the bone marrow is key to long-lived memory, but the underlying mechanisms are still unclear.This article proposes that recirculating memory T cells are maintained within two types of niche in the bone marrow, that is, the ‘self-renewal’ and the ‘quiescence’ niche, resembling those for hematopoietic stem cells.