Novel CD8+ T-Cell Subsets Demonstrating Plasticity in Patients with Inflammatory Bowel Disease.
Distinct CD8+ T-cell subsets such as interleukin-17-expressing Tc17 and Foxp3-expressing Tcreg are functionally similar to CD4+ T cells. Though CD4+ T cells are dysregulated in patients with inflammatory bowel disease (IBD), CD8+ T cells are not well investigated. Vitamin D is an environmental factor which influences T-cell subsets. We assessed the prevalence of CD8+ T-cell subsets among peripheral blood mononuclear cells (PBMC) and lamina propria mononuclear cells (LPMC) of patients with Crohn's disease, patients with ulcerative colitis, and healthy controls. We then tested the effect of 1α,25-dihydroxyvitamin D3 on CD8+ T-cell subsets.



A total of 73 patients with Crohn's disease, 49 patients with ulcerative colitis, and 47 healthy controls were studied. LPMC or PBMC were isolated and flow cytometry was performed. CD3+ T cells, isolated from PBMC, were cultured with or without 1α,25-dihydroxyvitamin D3, before flow cytometry.



In LPMC, the prevalence of Tcreg was higher in patients with IBD (P < 0.05), whereas Tc17 were higher in patients with ulcerative colitis compared with patients with Crohn's disease and healthy controls (P < 0.05). In PBMC, both Tcreg and Tc17 were higher in patients with IBD (P < 0.01). Double-expressing interferon-γ+ interleukin-17+ and Foxp3+ interleukin-17+ CD8+ T cells were also identified indicating possible CD8+ plasticity. 1α,25-dihydroxyvitamin D3 decreased interferon-γ-expressing Tc1 (P < 0.05), but had no effect on Tc17 or Tcreg.



The prevalence of novel CD8+ T-cell subsets is altered in patients with IBD. Double-expressing cells indicate plasticity and were identified in patients with IBD. Vitamin D may have a limited effect on CD8+ T cells by decreasing interferon-γ expression.
Departments of *Medicine, and †Biological Sciences, University of Calgary, Calgary, Alberta, Canada; ‡Department of Gastroenterology, Peking Union Medical College Hospital, Beijing, China; §Department of Production Animal Health, University of Calgary, Calgary, Alberta, Canada; and ‖Department of Gastroenterology and Hepatology, Massachusetts General Hospital, Boston, Massachusetts.
Michael R
MR
Tom
Ji
J
Li
Aito
A
Ueno
Miriam
M
Fort Gasia
Ronald
R
Chan
Daniel Y
DY
Hung
Shem
S
Chenoo
Marietta
M
Iacucci
Humberto B
HB
Jijon
Gilaad G
GG
Kaplan
Paul L
PL
Beck
Remo
R
Panaccione
Herman W
HW
Barkema
Andre G
AG
Buret
Vijay
V
Yajnik
Subrata
S
Ghosh
D000328:Adult; D000368:Aged; D001706:Biopsy; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000502:physiology*; D002117:Calcitriol / Q000494:pharmacology; D016022:Case-Control Studies; D000066670:Cell Plasticity / Q000187:drug effects; D002478:Cells, Cultured; D003093:Colitis, Ulcerative / Q000276:immunology* / Q000473:pathology; D003424:Crohn Disease / Q000276:immunology* / Q000473:pathology; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000473:pathology; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*; D058504:Th17 Cells / Q000502:physiology*; D014815:Vitamins / Q000494:pharmacology; D055815:Young Adult
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D020381:Interleukin-17; D014815:Vitamins; D007371:Interferon-gamma; D002117:Calcitriol