A novel large granular lymphocyte-like cell isolated from IL-2-supplemented murine intestinal lamina propria lymphocyte cultures with potent inhibitory action on lymphocyte proliferation.
Regulation and control of the local immune system in the gut mucosa are poorly understood phenomena. Recently we observed in whole alpha-CD3-driven, IL-2-supplemented, lamina propria (LP) T cell cultures that pronounced anergy developed concomitant with the appearance of large granular lymphocyte (LGL)-like cells. The LGL-like cells did not appear in the cultures in the absence of alpha-CD3 activation. These cells expressed Thy 1.2, NK1.1, AsGM1, CD3, and most often CD8 but were always negative for CD4. They exclusively required IL-2 to proliferate and survive in culture and several cell lines were established. Analysis of the regulatory ability of these cells on immune responses revealed that the gut LGL-like cells strongly inhibited T as well as B cell proliferation by releasing a soluble factor(s). Subsequent detection in the culture supernatants of cytokines with reported inhibitory properties on lymphocyte proliferation, interferon-gamma, and transforming growth factor beta correlated poorly to the inhibitory action of the supernatants. Despite the NK-like nature of these cells no or weak cytotoxic activity could be detected against Yac-1 target cells. The LGL-like cells expressed Fc receptors for IgE and demonstrated properties in EM and cytochemical analysis which resembled mucosal mast cells, but unlike such cells the LGL-like cells did not contain histamine or serotonin. The lamina propria of normal mouse small intestine was found to contain cells with morphology and staining pattern similar to those of cultured LGL-like cells, i.e., double-positive for Thy 1.2 and NK 1.1. We propose that this novel intestinal LGL-like cell, probably of T cell origin, may act as a potent suppressive cell in mucosal immune responses exerting a regulatory function on T cell activities and preventing adverse inflammatory reactions in the intestinal mucosa. Therefore, we suggest that these cells may be referred to as granulated inhibitory lymphocytes (GIL) cells. The lamina propria GIL cells exhibit many similarities to the recently described immunosuppressive decidual LGL cells in the placenta.
Department of Medical Microbiology, University of Göteborg, Sweden.
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Hörnqvist
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Enerbäck
X J
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Chen
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Lycke
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D016130:Immunophenotyping; D007376:Interleukin-2; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology
D016207:Cytokines; D007376:Interleukin-2