CD8+ regulatory T-cells for use in the treatment of inflammatory disorders of the human gastrointestinal tract

A method of treating an inflammatory or autoimmune disease of the gastrointestinal tract, comprising administering to a subject in need thereof a pharmaceutical composition consisting essentially of an isolated CD8+ Treg cell population, wherein the administered cells consist of CD8+ Treg cells having the following signatures:

• (i) a signature that identifies that the Treg cells are CD8+ regulatory T cells selected from CD8+, CD8+CD122+, CD8+Y, or CD8+CD122+Yn, wherein n indicates that one or more Y signatures is present,
• (ii) a signature that identifies that the Treg cells are mucosal tissue type tropic that can migrate to diseased mucosal tissue of the gastrointestinal tract, selected from α4β7+, α4β7+, α4β7+Xn, or α4β7+Xn, wherein n indicates that one or more X signatures is present,
• (iii) optionally, a signature CCR9+ that identifies that the Treg cells are homing cells tropic with respect to diseased mucosal tissue of the gastrointestinal tract,
• (iv) a signature that identifies that the Treg cells are antigen-experienced emigrant cells that originate from target mucosal tissue of the gastrointestinal tract, selected from CD62L−, Xn, Yp, XnYp, CD62L−Xn, CD62L−Yp, and CD62L−XnYp, wherein n and p indicate that one or more X signatures and/or one or more Y signatures, respectively, is present, and
• (v) optionally, a signature α4+αE+β7Hi that identifies that the Treg cells are capable of being retained in the target mucosal tissue of the gastrointestinal tract,
• wherein an X signature indicates that the Treg cells can localize, have emigrated from, or are marked for preferential retention in the specific part of the gastrointestinal tract that is diseased, and is one or more selected from CD49d+, CD54+, CD99−, CD99R+, CD166+, CD49a−, CD49c−, CD49f−, CD102−, CD165+, CDw328−, CDw329−, CD37−, CD38−, and CD49e−;
• and
• a Y signature indicates immunosuppressive regulatory function, and is one or more selected from CD25+, CD58+, CD73+, CD95+, CD105+, CD107a+, CD107b+, CD122+, CD244+, CD268+, CD274+, CD31−, CD35+, CD39+, CD41a+, CD63+, CD85−, CD88+, CD97+, CD108+, CD120b+, CD127+, CD130−, CD132+, CD151+, CD210+, CD221−, CD226+, CD335−, CD336−, EGF-R−, CD66−, CD126−, CD150+, CD161+, CD195+, CD200−, and CD279+;
• wherein the isolated CD8+ Treg cell population has T-cell receptor clonal diversity restricted to clonotypes specific for antigens present in the mucosal tissue types to which the selected signatures relate.