Peripheral T cells in the thymus: have they just lost their way or do they do something?

Abstract

In young adult mice, the thymus produces about a million newly formed T cells every day that colonize peripheral lymphoid tissues. Mostly regarded as a primary lymphoid organ only, the relationship between the thymus and peripheral lymphoid organs is considered unidirectional. However, this perception has been challenged by reports showing that peripheral lymphocytes, mostly T cells, can migrate back into the thymus. The presence of recirculating T cells in the thymus is rather incongruous and raises the question: is the presence of ‘peripheral’ T cells in the thymus superfluous or do these cells fulfill some relevant physiologic functions? There is now evidence that cells of the hematopoietic lineage, including T cells, can play an active role during thymocyte selection, a role generally considered the exclusive property of thymic epithelial cells and dendritic cells. Although, on a per cell basis, peripheral T cells in the thymus may be less efficient than thymus epithelial cells or dendritic cells at thymocyte positive and negative selection, they may nevertheless contribute to selection by influencing the selectable TCR repertoire and post‐selection T cell functionality. Here, peripheral lymphocytes re‐entering the thymus may be envisioned as Trojan horses as these cells may introduce antigens necessary for both positive and negative selection of T cells.

Features of Human CD3+CD20+ T Cells

“…Within the thymus we detected this T cell population within the mature, CD4 or CD8 single positive medullary T cell population. This might indicate that these cells originate from the thymus, although also evidence for a migration from mature T cells back to the thymic medulla has been reported (18,19).…”

Thymic homing of activated CD4+ T cells induces degeneration of the thymic epithelium through excessive RANK signaling

“…Once homing to the thymus, they are predominantly localized in the medulla and remain there for prolonged periods 33 . It is estimated that the thymus of an adult mouse can accommodate about 10 5 recirculating peripheral T cells 35–37 . Despite the relatively constant number, the proportion of such cells increases dramatically with age, accounting for more than 20% of single positive (SP) thymocytes in mice over 1 year of age 37 .…”

“…Is the presence of peripheral T cells in the thymus merely an epiphenomenon or are they destined to fulfill some relevant physiological functions ? Despite controversy, evidence is emerging that these cells may participate in the shaping of the T cell repertoire by delivering self antigens into the thymus 35, 36, 38–40 .…”

Peripheral T Cells Re-Enter the Thymus and Interfere with Central Tolerance Induction

“…More recently, several reports showed that back-migration can occur, and mature peripheral T cells may re-enter the thymus (2)(3)(4)(5). Apparently, ∼10…”

“…5 mature T cells from the periphery can be accommodated in a specific thymic niche (3) and mainly localize to the medulla (6). Multiple possible functions have been assigned to these cells, such as maintenance of medullary thymic epithelial cells (mTECs) or direct mediation of thymocyte selection in certain experimental settings (7)(8)(9)(10).…”