Thymus‐resident memory CD8⁺T cells mediate local immunity

Abstract

T cells by antibodies further revealed that thymic virus-specific memory CD8+ T cells did not belong to the circulating pool of lymphocytes. Finally, we demonstrate that these thymus-resident virus-specific memory CD8 + T cells efficiently mounted a secondary proliferative response, exhibited immediate effector functions and were able to protect the thymus from lymphocytic choriomeningitis virus reinfection. In conclusion, the present study not only describes for the first time virus-specific memory CD8 + T cells with characteristics of tissue-resident memory T (T RM ) cells in a primary lymphoid organ but also extends our knowledge about local T-cell immunity in the thymus.Keywords: CD69 r CD103 r E-cadherin r Tissue-resident memory T (T RM ) cells r Viral infections See accompanying Commentary by Mackay and GebhardtAdditional supporting information may be found in the online version of this article at the publisher's web-site IntroductionCirculating memory T cells are usually separated into two main populations defined by their expression of lymph node homing molecules: central memory T (T CM ) cells and effector memory T (T EM ) cells [1]. T CM cells have a high proliferative potential and express CCR7/CD62L that allows them to traffic between the secondary lymphoid organs to maintain the memory T-cell pool. T EM cells lack lymph node homing receptors and circulate between Correspondence: Prof. Hanspeter Pircher e-mail: hanspeter.pircher@uniklinik-freiburg.de the blood and extralymphoid organs to patrol the body [2]. Some regions in the body, however, are excluded from immune surveillance by circulating memory T cells, namely peritoneal cavity, gut, and brain as shown by parabiosis experiments [3]. More recently, a third main memory T-cell population that persists in peripheral organs after viral infections to secure immediate local defense after pathogen reencounter has been identified in humans and mice [4,5]. These memory T cells are called tissue-resident memory T cells (T RM cells) and are not replenished from the circulation. Beside the lack of recirculation, the expression of CD103 and CD69 and local antigen-independent persistence are characteristics of T RM cells [4]. T RM cells have so far been described in Eur. J. Immunol. 2013. 43: 2295-2304 the gut, skin, brain, sensory ganglia, vagina, lungs, and salivary glands [4,[6][7][8][9][10]. These tissues are mostly surface lining and either epithelial or neuronal derived with anatomical border layers like basement membranes or the blood-brain barrier, and therefore, more difficult to be patrolled by circulating cells. Another epithelial-derived organ is the thymus, a primary lymphoid organ in which T-cell differentiation takes place [11]. During maturation, T cells undergo positive and negative selection eliminating useless and most harmful T cells. These selection processes depend on TCR interactions with self-MHC molecules presenting peptide antigens expressed in the thymus. Therefore, the expression of antigen within the thymus has to be tightly con...

Cutting Edge: Resident Memory CD8 T Cells Occupy Frontline Niches in Secondary Lymphoid Organs

“…T RM have been identified in many non-lymphoid tissues as well as the thymus, where they are positioned to rapidly provide protection against pathogens re-encountered at anatomic barriers (4, 5, 7, 11, 20). T RM express unique phenotypic signatures that distinguish them from recirculating T CM and T EM , particularly CD69 expression (4, 8, 17).…”

Immunological memories of the bone marrow

“…It is interesting to note that in the recent hype about “tissue‐resident” memory T lymphocytes, bone marrow‐resident memory T lymphocytes were largely disregarded, quasi the “Cinderella” of memory lymphocytes 154, 155, 156, 157, 158, 159…”

“…In peripheral tissues and in the bone marrow, the numbers of experienced T cells recognizing a particular antigen remain high over time, while numbers of their circulating counterparts drop. Populations of “tissue‐resident”, antigen‐experienced T cells of lung, gut, brain, thymus, and skin express CD103 (αE integrin) and CD69 154, 155. CD103 mediates binding to E‐cadherin, which is expressed on epithelial cells 161.…”

Tissue-Resident T Cells: Dynamic Players in Skin Immunity

“…Populations of T RM have also been described in other tissues including the small intestine (29, 30), vaginal mucosa (18, 31), brain (32, 33), lung (34), salivary glands (35), and thymus (36). These cells can be identified by high expression of the α E integrin chain (CD103) and the marker CD69 (19).…”