Expansion of CD8+ T cells with regulatory function after interaction with intestinal epithelial cells.
OBJECTIVE
Regulatory T cells play a role in the control of immune responses in the intestinal mucosa and their absence may predispose to inflammatory bowel disease (IBD). We have previously shown that T cells activated by intestinal epithelial cells (IECs) are suppressive in function. Our goal was to characterize the phenotype and function of T cells proliferating after interaction with IECs.


METHODS
Irradiated human IECs, isolated from normal resection specimens, were cultured with carboxy fluorescein succinimidyl ester (CFSE) labeled T cells. Flow cytometric analysis of T cells was performed at days 5-10. CD8+ T cells proliferating in culture with IECs were sorted and added to suppressive assays.


RESULTS
The precursor frequency of T cells proliferating in response to IECs ranged from 0.3%-0.9%. Several subpopulations were shown to proliferate (CD8+CD28-/CD8+CD28+/CD4+CD25+), but one population (CD8+CD28-CD101+CD103+) appeared to be dependent on contact with the CD8 ligand gp180. After sorting, culture in the presence of interleukin (IL)-7 and IL-15 allowed for the generation of cell lines. IEC-activated CD8+ T cells, but not nonactivated CD8+ T cells, were suppressive in function. Suppression belonged to the CD101+CD103+ subset of IEC-activated CD8+ T cells and appeared to require cell contact. CD8+ lamina propria T cells also showed suppressive function, suggesting the presence of CD8+ regulatory T cells in the mucosa.


CONCLUSIONS
IECs are able to induce the proliferation of a small fraction of CD8+ peripheral T cells. The CD8+CD28- subset of IEC-activated CD8+ T cells, which express CD101 and CD103, interacts with IECs through gp180 and has regulatory function.
Allez
Matthieu
M
Immunobiology Center, Mount Sinai School of Medicine, New York, New York 10029, USA. matthieu_allez@mssm.edu
Brimnes
Jens
J
Dotan
Iris
I
Mayer
Lloyd
L
D015703:Antigens, CD / Q000378:metabolism; D015415:Biomarkers; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000502:physiology*; D002450:Cell Communication / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D006801:Humans; D039001:Integrin alpha Chains / Q000378:metabolism; D007413:Intestinal Mucosa / Q000166:cytology / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000378:metabolism / Q000502:physiology; D010641:Phenotype; D016176:T-Lymphocyte Subsets / Q000166:cytology
D015703:Antigens, CD; D015415:Biomarkers; C093213:CD101 antigen, human; D039001:Integrin alpha Chains; D008562:Membrane Glycoproteins; C091367:alpha E integrins; C030340:elastin microfibril interface located protein