Activation of intra-epithelial lymphocytes; their morphology, marker expression and ultimate fate

Intraepithelial lymphocytes (IELs) have been considered to play a key role in the defense system of the small intestine. Its mechanism has not been made sufficiently clear. Studies on IELs have been extremely limited to functions of alpha beta T-cell receptor (alpha beta TCR) IELs (alpha beta-IELs). Since, in the mouse duodenum and jejunum, gamma delta-IELs consist 75 % of IELs, it thus would be inappropriate to argue the mechanism without extensive discussions over the functions of gamma delta-IELs. In previous studies, we found that the anti-CD3 monoclonal antibody (mAb) injection induced DNA fragmentation in intestinal epithelial cells (IECs) and DNA repair immediately after, that these responses were reproduced by anti-gamma delta TCR mAb not by anti-alpha beta TCR mAb and that the DNA fragmentation was induced by Granzyme B secreted by IELs, totally independent of Perforin. To further explore the functions of IELs in situ, we undertook experiments exclusively focused on IELs, on their changes and ultimate fate after the stimulation in mouse in vivo system. The current study demonstrated that the injected anti-CD3 mAb bound to CD3 on IELs, that the mAb activated gamma delta-IELs, leading to their degranulation, that changes occurred irreversibly in IELs and finally that activated IELs died in situ. gamma delta-IELs could be considered to respond to various stimulations most likely without the need of accessory cells (always ready for rapid response), to die in situ (disposable) and thus to respond to the stimulation only once (a one-shot responder). These characteristics of gamma delta-IELs are important to further elucidate the functions of gamma delta-IELs in the intestinal defense system.