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Changes in Human Mucosal γδ T Cell Repertoire and Function Associated with the Disease Process in Inflammatory Bowel Disease

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Abstract

Background

Although γδ T cells are a major component of the human intestinal mucosa, it is not clear what role they play in mucosal immunity or if they are involved in the disease process of inflammatory bowel disease (IBD).

Materials and Methods

Flow cytometry and reverse transcriptase-polymerase chain reaction (RT-PCR) assays were used to identify quantitative and qualitative changes in the repertoire of γδ T cells present in surgical and/or biopsy samples of normal and inflamed colon from individual patients with ulcerative colitis (UC) or Crohn’s disease (CD). Cytokine production and the ability to adhere to and interact with colonic fibroblasts were used to compare the functional properties of γδ T cells isolated from the normal and diseased colonic mucosa.

Results

Increased numbers of γδ T cells localized in areas of inflammation and tissue injury were found in the majority of patients, irrespective of the type of IBD present. This expansion was attributable to an increase in Vδ1+ cells expressing a Vδ1-(Dδ3)-Jδ1-encoded T cell receptor and was seen in patients with severe disease as well as those with newly diagnosed or less severe forms of IBD. Among T cells present in the inflamed mucosa of patients with CD, γδ T cells, particularly Vδ1+ cells, were a major source of the proinflammatory cytokine interferon-γ and could interact with colonic fibroblasts.

Conclusions

Our results demonstrate that the chronic inflammatory immune response characteristic of IBD is associated with distinct changes in the number, distribution, composition, and function of mucosal γδ T cells. Through the production of cytokines and physical interaction with other cells, γδ T cells can perform an immunoregulatory function and contribute to the pathophysiology of IBDs.

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Acknowledgements

We are grateful to Ms. Linda Hurd for compiling pertinent data on IBD and normal patients in this study. We thank William G. Crowley for expert technical assistance. This work was supported by grants from the American Cancer Society (JFRA 399) and the National Institutes of Health (AI 31972) to S.R.C. L.D.M. was supported in part by a National Institutes of Health Training Grant (5-T32-CA-09140-20) and a Crohn’s and Colitis of America (CCFA) Fellowship.

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  1. Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, 19104-6021, USA

    Laila D. McVay, Baiqing Li, Renée Biancaniello, Mary Anne Creighton & Simon R. Carding

  2. Division of Gastroenterology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, 19104-6021, USA

    Dale Bachwich & Gary Lichtenstein

  3. Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, 19104-6021, USA

    John L. Rombeau

  4. Department of Microbiology, 802F Abramson Center, 34th Street & Civic Center Blvd., Philadelphia, Pennsylvania, 19104, USA

    Simon R. Carding

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  1. Laila D. McVay
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Correspondence to Simon R. Carding.

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McVay, L.D., Li, B., Biancaniello, R. et al. Changes in Human Mucosal γδ T Cell Repertoire and Function Associated with the Disease Process in Inflammatory Bowel Disease. Mol Med 3, 183–203 (1997). https://doi.org/10.1007/BF03401672

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