Methods and compositions for modulating peripheral immune function

Abstract

Disclosed herein are cell preparations useful for modulating various peripheral immune functions, methods for making said cell preparations, and methods for their use.

What is claimed is: 
     
       1. A method for modulating production of one or more cytokines by a T-lymphocyte (T-cell) or a monocyte; the method comprising:
 contacting the T-cell or monocyte with an effective amount of SB623 MASC-derived immune modulatory cells; 
 wherein said contacting results in stimulation of the production of one or more anti-inflammatory cytokines and/or inhibition of production of one or more pro-inflammatory cytokines by the T-cell or the monocyte; 
 further wherein said SB623 MASC-derived immune modulatory cells are obtained by 
 (a) providing a culture of marrow adherent stromal cells (MASCs); 
 (b) contacting the cell culture of step (a) with a polynucleotide comprising sequences encoding the Notch intracellular domain (NICD) wherein said polynucleotide dos 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, such that said marrow adherent stromal cells are induced to form SB623 MASC-derived immune modulatory cells by expression of the NICD. 
 
     
     
       2. The method of  claim 1 , wherein the pro-inflammatory cytokine is interferon gamma (IFN-γ). 
     
     
       3. The method of  claim 1 , wherein the pro-inflammatory cytokine is tumor necrosis factor alpha (TNF-α). 
     
     
       4. The method of  claim 1 , wherein the anti-inflammatory cytokine is interleukin-10 (IL-10). 
     
     
       5. The method of  claim 1 , wherein the T cell is a helper T-cell. 
     
     
       6. The method of  claim 5 , wherein the helper T-cell is T H 1 cell. 
     
     
       7. The method of  claim 1 , wherein the T-cell is a regulatory T-cell. 
     
     
       8. The method of  claim 7 , wherein the regulatory T-cell is a T R 1 cell. 
     
     
       9. The method of  claim 1 , wherein said modulation of cytokine production results in conversion of a T-cell population from one that is pro-inflammatory to one that is anti-inflammatory.