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

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Abstract

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 αβ T-cell receptor (αβTCR) IELs (αβ-IELs). Since, in the mouse duodenum and jejunum, γδ-IELs consist 75 % of IELs, it thus would be inappropriate to argue the mechanism without extensive discussions over the functions of γδ-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-γδTCR mAb not by anti-αβTCR 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 γδ-IELs, leading to their degranulation, that changes occurred irreversibly in IELs and finally that activated IELs died in situ. γδ-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 γδ-IELs are important to further elucidate the functions of γδ-IELs in the intestinal defense system.

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Acknowledgements

This work was in part supported by a Grant-in-aid for Scientific Research from the Ministry of Education, Science and Culture, Japan (20590181 to M.O. and 21590207 to T.I.) and the Japan Science and Technology Agency (JST).

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Authors and Affiliations

  1. Division of Immunology and Embryology, Department of Cell Biology, Tohoku University School of Medicine, 980-8575, Sendai, Japan

    Masaki Ogata, Yuta Ota & Tsunetoshi Itoh

  2. Department of Applied Research, Division of Immunology, Yakult Central Institute for Microbiological Research, Tokyo, Japan

    Masanobu Nanno

  3. Department of Rheumatology and Clinical Immunology, Clinical Research Center for Allergy and Rheumatology, Sagamihara National Hospital, Sagamihara, Japan

    Ryuji Suzuki

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  1. Masaki Ogata
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  2. Yuta Ota
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  5. Tsunetoshi Itoh
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Correspondence to Masaki Ogata.

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Ogata, M., Ota, Y., Nanno, M. et al. Activation of intra-epithelial lymphocytes; their morphology, marker expression and ultimate fate. Cell Tissue Res 356, 217–230 (2014). https://doi.org/10.1007/s00441-013-1786-4

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