CD4
The invention provides CD4 + CD25 − T cells and Tr1-like regulatory T cells (i.e., contact-independent Type 1-like regulatory T cells), processes for their production and their use for regulatory purposes.
1. A method for producing a pharmaceutical composition comprising human Tr1-like regulatory cells which comprises:
(i) activating CD4 + CD25 + T cells to produce activated CD4 + CD25 + T cells by subjecting unactivated CD4 + CD25 + T cells to an activation stimulus selected from the group consisting of (a) and (b), wherein (a) is a combination of plate-bound anti-CD3 and soluble anti-CD28 antibodies; and (b) are allogeneic mature dendritic cells;
(ii) anergizing CD4 + CD25 − T cells by contacting the CD4 + CD25 − T cells ex vivo with an anergic state inducing agent consisting of said activated CD4 + CD25 + T cells and said activation stimulus to yield human Tr1-like regulatory cells from said CD4 + CD25 − T cells; and thereafter
(iii) formulating a pharmaceutical composition comprising said human Tr1-like regulatory cells.
2. The method of claim 1 , wherein said contacting comprises coculturing the CD4 + CD25 − T cells with the CD4 + CD25 + T cells.
3. The method of claim 1 , wherein said Tr1-like regulatory cells produce IL-10.
4. The method of claim 3 , wherein said Tr1-like regulatory cells suppress the proliferation of syngeneic CD4 + T cells.