Molecular mechanisms of CD8+ T cell trafficking and localization

Abstract

Cytotoxic CD8+ T cells are potent mediators of host protection against disease due to their ability to directly kill cells infected with intracellular pathogens and produce inflammatory cytokines at the site of infection. To fully achieve this objective, naïve CD8+ T cells must be able to survey the entire body for the presence of foreign or “non-self” antigen that is delivered to draining lymph nodes following infection or tissue injury. Once activated, CD8+ T cells undergo many rounds of cell division, acquire effector functions, and are no longer restricted to the circulation and lymphoid compartments like their naïve counterparts, but rather are drawn to inflamed tissues in order to combat infection. As CD8+ T cells transition from naïve to effector to memory populations, this is accompanied by dynamic changes in the expression of adhesion molecules and chemokine receptors that ultimately dictate their localization in vivo. Thus, an understanding of the molecular mechanisms regulating CD8+ T cell trafficking and localization are critical for vaccine design, control of infectious diseases, treatment of autoimmune disorders, and cancer immunotherapy.

Immune Checkpoints in Circulating and Tumor-Infiltrating CD4+ T Cell Subsets in Colorectal Cancer Patients

“…Potent anti-tumor immune responses require a shift in balance between levels of Tregs and T effector cells (Teff) in the TME (18). Therefore, T cell trafficking and localization into tumor sites and preferential proliferation and differentiation of tumorreactive T cells can facilitate effective immunotherapies (19). Moreover, T cell inflamed tumors, characterized by existing antitumor T cell responses, are associated with improved clinical outcomes in CRC patients (11,20).…”

Development of a novelFrancisella tularensisLive Vaccine Strain expressing ovalbumin provides insight intoFrancisella tularensis-specific CD8+T cell responses

“…Upon activation, naïve CD8 + T cells differentiate into effector and memory subsets. Effector/memory (T EM ) CD8 + T cells are characterized by the decreased expression of markers associated with lymphoid tissue homing (eg: CD62L) and increased expression of markers associated with homing to the source of inflammation (eg: CD44) [41]. These cells have a high propensity for effector functions, including killing infected cells and producing cytokines.…”

“…These cells have a high propensity for effector functions, including killing infected cells and producing cytokines. Central memory (T CM ) cells are less geared towards effector functions; rather they retain extensive proliferative capacity, and primarily circulate through the secondary lymphoid organs due to high expression of CD62L and other lymphoid tissue homing markers [41]. The primary role of T CM is generally considered to be their ability to rapidly expand into a new population of effector cells upon re-exposure to antigen [42,43].…”

A T-limfociták bőrbe vándorlása, a bőr mint immunszerv T-sejtes homeosztázisa

“…A szállításban az úgynevezett antigénprezentáló sejtek, például Langerhans-vagy dendritikus sejtek vesznek részt. Ezek a sejtek gyakran igen nagy sűrűségben vannak jelen a bőr különböző rétegeiben, és folyamatosan szondázzák a környezetüket, azzal a céllal, hogy ezeket a megjelenő antigéneket beszállítsák a környéki nyirokcsomókba, és bemutassák az oda belépő T-sejteknek (Nolz et al, 2011).…”

“…A vándorlás szabályozása három kiemelt területen történik: a) az érhálózat mikrovaszkuláris területein, ahol a sejtek transzendothéliális migrációval elhagyják a véráramot, b) a kemokineket termelő sejteknél, ahol a T-sejtek kapcsolatba léphetnek a célsejtekkel, illetve c) a nyirokrendszernél, ahol a sejtek képesek elhagyni az egészséges vagy gyulladt szövetet. Sajnos a mai napig nagyon keveset tudunk a T-sejtek, illetve azok alcsoportjainak homingjáról és szabályozásáról, illetve kevés olyan markerrel rendelkezünk, amely csak egy szövetbe történő vándorláshoz, illetve csak egy fajta sejttípuson jelenne meg, így specifikálva a különböző homing folyamatokat (Nolz, 2015).…”