Methods and compositions for modulating peripheral immune function

1. A method for inhibiting a peripheral inflammatory response in a subject, the method comprising

administering to the subject an effective amount of cells obtained by a method comprising:

(a) providing a culture of marrow adherent stromal cells;

(b) contacting the cell culture of step (a) with a polynucleotide comprising sequences encoding a Notch intracellular domain (NICD) wherein said polynucleotide does not encode a full-length Notch protein:

(c) selecting cells that comprise the polynucleotide of step (b); and

(d) further culturing the selected cells of step (c) in the absence of selection for the polynucleotide;

wherein inhibition of the peripheral inflammatory response is mediated by one or more of:

(i) inhibition of helper T-cell proliferation;

(ii) expansion of a regulatory T-cell population;

(iii) inhibition of differentiation of a monocyte to a dendritic cell;

(iv) inhibition of dendritic cell maturation;

(v) alteration of the cytokine profile of a T-cell or a monocyte from one that is pro-inflammatory to one that is anti-inflammatory; and

(vi) reduced production of interleukin-10 (IL-10) by a T-cell or a monocyte.

2. The method of claim 1 , wherein said inhibiting a peripheral inflammatory response comprises inhibition of activation of peripheral T-cells.

3. The method of claim 2 , wherein said activation of peripheral T-cells comprises expression of CD69 by the T-cells; expression of HLA-DR by the T-cells, or expression of both CD69 and HLA-DR by the T-cells.

4. The method of claim 2 , wherein said activation of peripheral T-cells comprises proliferation of CD4 + T-cells.

5. The method of claim 1 , wherein said helper T-cell proliferation, or said production of IL-10 by a T-cell, is associated with the pathology of rheumatoid arthritis.

6. The method of claim 1 , wherein said dendritic cell maturation comprises an increase in expression of CD86 by the dendritic cell.

7. The method of claim 1 , wherein the peripheral inflammatory response results from an allogeneic transplantation, ischemia or necrosis.

8. The method of claim 1 , wherein the peripheral inflammatory response results from graft-versus-host disease (GVHD) or graft rejection.

9. The method of claim 1 , wherein the peripheral inflammatory response results from an autoimmune disorder.

10. The method of claim 9 , wherein the autoimmune disorder is selected from the group consisting of multiple sclerosis, ulcerative colitis, chronic obstructive pulmonary disease (COPD), asthma, lupus and Type I diabetes.