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 of suppressing the proliferation of human CD4 + T cells ex vivo or in vivo comprising the steps of:
(a) isolating CD4 + CD25 + T cells from human peripheral blood;
(b) anergizing human CD4 + CD25 − T cells by contacting the CD4 + CD25 − T cells ex vivo with an anergic state inducing agent consisting of the CD4 + CD25 + T cells and an activation stimulus, whereby Tr-1 like regulatory cells are produced, wherein the activation stimulus is selected from the group consisting of (i) and (ii), wherein (i) is a combination of anti-CD3 and anti-CD28 antibodies; and (ii) is mature dendritic cells; and
(c) suppressing the proliferation of said CD4 + T cells by (i) introducing said Tr-1 like regulatory cells to a composition comprising said CD4 + T cells ex vivo or (ii) administering said Tr-1 like regulatory cells to a human subject in vivo.
2. The method of claim 1 , wherein step (b) of the method of producing said Tr-1 like regulatory cells comprises co-culturing the CD4 + CD25 − cells with CD4 + CD25 + cells ex vivo and wherein said Tr1-like regulatory cells produce IL-10.
3. The method of claim 1 , wherein said Tr-1 like regulatory cells are administered to a human subject.
4. The method of claim 3 , wherein said administration is to treat graft versus host disease in said human subject.