An accessory role of TCRγ δ+ cells in the exacerbation of inflammatory bowel disease in TCRα mutant mice

Abstract

T cell receptor α mutant (TCRα –/–) mice, which spontaneously develop colitis under conventional conditions, did not show any signs of colitis under germ‐free conditions, leaving TCRα –β + cells (β dim cells) and TCRγ δ + cells much reduced. Moreover, TCRα –/– mice with alymphoplastic mutation (aly/aly TCRα –/– mice), which lack Peyer's patches and peripheral lymph nodes, did not suffer from colitis. While both β dim cells and TCRγ δ + cells were present in the colons of aly/aly TCRα –/– mice and aly/+ TCRα –/– mice, cytotoxicity of colonic TCRγ δ + cells in aly/aly TCRα –/– mice was almost abolished. Transfer of TCRγ δ + cells from TCRα –/– mice into scid/scid mice or aly/aly TCRα –/– mice could not induce colitis, but injection of anti‐TCRδ mAb into TCRα –/– mice prevented colitis from developing. Finally, TCRα –/– mice expressing transgenic (Tg) KN6‐TCRγ δ hardly developed colitis, accompanied by colonization of non‐cytotoxic Tg TCRγ δ + cells in their colonic mucosa. These results demonstrate that intestinal resident TCRγ δ + cells may be involved in the exacerbation of inflammatory bowel disease in TCRα –/– mice.

Essential Roles of IL-6 Trans-Signaling in Colonic Epithelial Cells, Induced by the IL-6/Soluble–IL-6 Receptor Derived from Lamina Propria Macrophages, on the Development of Colitis-Associated Premalignant Cancer in a Murine Model

“…In this study, we observed the activation NFkB in the colonic mucosa during the development of CApC and its inhibition by the sgp130Fc protein. It has been widely reported that enteric bacteria are necessary for the induction of chronic intestinal inflammation in various mouse model (14,45,46). The increased presence of mucosal adherent bacteria and the intramucosal translocation of enteric bacteria are usually observed in these models (47).…”

Intestinal γδ T Cells Develop in Mice Lacking Thymus, All Lymph Nodes, Peyer’s Patches, and Isolated Lymphoid Follicles

“…TCR-␥␦ (KN6)-Tg mice on the BALB/c background were described previously (40). Female KN6-Tg mice were crossed with scid/scid mice to generate KN6 scid/ϩ mice, then they were backcrossed with scid/scid mice to obtain KN6 scid/scid mice.…”

Intra- and Intercompartmental Movement of γδ T Cells: Intestinal Intraepithelial and Peripheral γδ T Cells Represent Exclusive Nonoverlapping Populations with Distinct Migration Characteristics

“…gd iIELs are specialized T cells that ensure the homeostasis of the intestinal epithelium (1-3) and protect against intestinal inflammation (4)(5)(6)(7)(8). Recent studies have shown that gd iIELs are involved in restricting the mucosal penetration of symbiotic microbiota (9) and in the preservation of epithelial tight junctions during intestinal infection (10,11).…”