Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 Nov;170(2):122-30.
doi: 10.1111/j.1365-2249.2012.04649.x.

Skin- and gut-homing molecules on human circulating γδ T cells and their dysregulation in inflammatory bowel disease

E R Mann  1 , N E McCarthy, S T C Peake, A N Milestone, H O Al-Hassi, D Bernardo, C T Tee, J Landy, M C Pitcher, S A Cochrane, A L Hart, A J Stagg, S C Knight
Affiliations

Skin- and gut-homing molecules on human circulating γδ T cells and their dysregulation in inflammatory bowel disease

E R Mann et al. Clin Exp Immunol. 2012 Nov.

Abstract

Changes in phenotype and function of γδ T cells have been reported in inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). Dysregulation of lymphocyte migration plays a key role in IBD pathogenesis; however, data on migratory properties of γδ T cells are scarce. Human circulating γδ T cells from healthy controls (n = 27), patients with active CD (n = 15), active UC (n = 14) or cutaneous manifestations of IBD (n = 2) were characterized by flow cytometry. Circulating γδ T cells in healthy controls were CD3(hi) and expressed CD45RO. They expressed gut-homing molecule β7 but not gut-homing molecule corresponding chemokine receptors (CCR)9, or skin-homing molecules cutaneous lymphocyte-associated antigen (CLA) and CCR4, despite conventional T cells containing populations expressing these molecules. CCR9 expression was increased on γδ T cells in CD and UC, while skin-homing CLA was expressed aberrantly on γδ T cells in patients with cutaneous manifestations of IBD. Lower levels of CD3 expression were found on γδ T cells in CD but not in UC, and a lower proportion of γδ T cells expressed CD45RO in CD and UC. Enhanced expression of gut-homing molecules on circulating γδ T cells in IBD and skin-homing molecules in cutaneous manifestations of IBD may be of clinical relevance.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Identification of human circulating γδ T cells and levels of CD3 expression. (a) Identification of γδ T cells from peripheral blood mononuclear cells (PBMC) according to fluorescence activated cell sorter (FACS) plots of forward- and side-scatters, and subsequent CD3 histogram and γδ T cell receptor (TCR) histogram. This example is from a healthy control. γδ T cells comprised 5·2 ± 0·9% (n = 27) of the total circulating T cell population. (b) FACS histograms demonstrating γδ T cells (red) back-gated onto the CD3 peak using WinList™ software, and summary graphs demonstrating mean fluorescence intensity (MFI) of CD3 staining of total circulating T cells compared with γδ T cells (n = 27). Histograms are representative of 27 independent experiments and were compared to isotype-matched controls. Paired t-test was applied. A P-value < 0·05 was considered statistically significant (*P < 0·05; **P < 0·01; ***P < 0·001).
Fig. 2
Fig. 2
Expression of gut- and skin-homing markers on γδ T cells. (a) Fluorescence activated cell sorter (FACS) histograms demonstrating proportions of γδ T cells expressing β7 (93·9 ± 1·5%, n = 16) and corresponding chemokine receptor (CCR)9 (3·8 ± 1·4%, n = 11); comparison against total circulating T cells for expression of β7 (77·0 ± 1·3%, n = 16). (b) FACS histograms demonstrating proportions of γδ T cells expressing cutaneous lymphocyte-associated antigen (CLA) (0·8 ± 0·3%, n = 9), CCR4 (1·6 ± 0·6%, n = 8) and CCR10 (0·2 ± 0·1%, n = 5); comparison against total circulating T cells for expression of CLA (12·6 ± 1·8%, n = 15) and CCR4 (16·9 ± 1·6%, n = 10). Histograms are representative of several independent experiments performed with similar results and were compared to isotype-matched controls; t-test was applied. A P-value < 0·05 was considered statistically significant (*P < 0·05; **P < 0·01; ***P < 0·001). Error bars represent standard error of the mean, horizontal lines represent the mean.
Fig. 3
Fig. 3
Reduced CD3 levels on γδ T cells in Crohn's disease but not ulcerative colitis. (a) Fluorescence activated cell sorter (FACS) histograms demonstrating levels of CD3 expression via γδ T cells (red) back-gated onto the CD3 peak using WinList™ software in healthy controls, active Crohn's disease (CD) patients and active ulcerative colitis (UC) patients. Histograms are representative of several independent experiments. (b) Summary graphs demonstrating mean fluorescence intensity (MFI) of CD3 staining of total circulating T cells compared with γδ T cells in active CD patients (n = 8) and active UC patients (n = 9), and summary graph demonstrating ratio of γδ T cell CD3 mean fluorescence intensity (MFI): total T cells CD3 MFI in healthy controls (1·6 ± 0·1, n = 16), active CD (1·2 ± 0·1, n = 8) and active UC (1·6 ± 0·2, n = 9). For comparison of total T cells versusγδ T cells CD3 MFI within the same individuals, paired t-tests were applied. For comparison of γδ T cell : total T cell CD3 MFI ratios between healthy controls, active CD and active UC patients, unpaired t-tests were applied. A P-value < 0·05 was considered statistically significant (*P < 0·05; **P < 0·01; ***P < 0·001; ***P < 0·001). Error bars represent standard error of the mean, horizontal line represents the mean.
Fig. 4
Fig. 4
Increased proportion of corresponding chemokine receptors (CCR)9+γδ T cells in Crohn's disease (CD) and ulcerative colitis (UC). Proportions of circulating γδ T cells in healthy controls (3·8 ± 1·4%, n = 11), active CD patients (27·4 ± 5·9, n = 8) and active UC patients (21·4 ± 9·2%, n = 7) expressing gut-homing marker CCR9; t-test was applied. A P-value < 0·05 was considered statistically significant (*P < 0·05; **P < 0·01; ***P < 0·001). Error bars represent standard error of the mean, horizontal lines represent mean.
Fig. 5
Fig. 5
Reduced proportion of CD45RO+γδ T cells in Crohn's disease (CD) and ulcerative colitis (UC). Proportions of circulating γδ T cells in healthy controls (69·8 ± 4·4%, n = 22), active CD patients (31·4 ± 6·2%, n = 15) and active UC patients (32·1 ± 4·5%, n = 15) expressing CD45RO; t-test was applied. A P-value < 0·05 was considered statistically significant (***P < 0·001). Error bars represent standard error of the mean, horizontal lines represent mean.
Fig. 6
Fig. 6
Aberrant expression of cutaneous lymphocyte-associated antigen (CLA) on γδ T cells in erythema nodosum. (a) Fluorescence activated cell sorter (FACS) histograms demonstrating proportions of circulating γδ T cells in healthy controls (0·8 ± 0·3%, n = 9), active inflammatory bowel disease (IBD) (1·2 ± 0·4%, n = 15) and erythema nodosum (EN) with inactive IBD (9·6% and 5·7%, n = 2). Bottom row: EN post-steroids (1·3%, n = 1; pre-steroids was 9·6%) expressing CLA. Histograms are representative of several independent experiments performed with similar results, and were compared to isotype-matched controls; FACS dot-plot demonstrating proportions of circulating γδ T cells in EN co-expressing gut-homing marker β7 and skin-homing marker CLA, expressing β7 only, or expressing CLA only. All plots were compared to isotype-matched controls. (b) Photographs of shins of EN patient pre- and post-corticosteroids.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Tonegawa S, Berns A, Bonneville M, et al. Diversity, development, ligands, and probable functions of gamma delta T cells. Cold Spring Harbor Symposium. Quant Biol. 1989;54:31–44. - PubMed
    1. Jameson J, Ugarte K, Chen N, et al. A role for skin gammadelta T cells in wound repair. Science. 2002;296:747–9. - PubMed
    1. Boismenu R, Havran WL. Modulation of epithelial cell growth by intraepithelial gamma delta T cells. Science. 1994;266:1253–5. - PubMed
    1. Komano H, Fujiura Y, Kawaguchi M, et al. Homeostatic regulation of intestinal epithelia by intraepithelial gamma delta T cells. Proc Natl Acad Sci USA. 1995;92:6147–51. - PMC - PubMed
    1. Hayday A, Tigelaar R. Immunoregulation in the tissues by gammadelta T cells. Nat Rev Immunol. 2003;3:233–42. - PubMed

Publication types

MeSH terms