Isolation and use of human lymphoid organ-derived suppressive stromal cells

Abstract

A method for suppressing an immune response is provided. The method involves administration of isolated lymphoid tissue-derived suppressive stromal cells (LSSC) to a subject in need of such treatment in an amount effective to suppress the immune response in the subject. The invention also involves a method to isolate LSSC by digesting lymphoid tissue fragments using a combination of an enzyme mix and agitation and then collecting the LSSC. Pharmaceutical preparations comprising LSSC are also provided.

We claim: 
     
         1 - 22 . (canceled) 
     
     
         23 . A pharmaceutical preparation comprising a composition of isolated lymphoid tissue-derived suppressive stromal cells (LSSCs), wherein the LSSCs are fibroblastic reticular cells (FRCs). 
     
     
         24 . The pharmaceutical composition of  claim 23 , wherein the FRCs are isolated by treating lymphoid tissue fragments using one or more of a chemical, mechanical, and electrical cell separation process, and then by collecting the FRCs. 
     
     
         25 . The pharmaceutical composition of  claim 24 , wherein the isolated FRCs are expanded through cell culture. 
     
     
         26 . The pharmaceutical composition of  claim 23 , wherein the isolated FRCs are ex vivo expanded cells. 
     
     
         27 . The pharmaceutical composition of  claim 23 , wherein the isolated FRCs are expanded by growing the collected cells until the FRCs are substantially free of non-LSSCs. 
     
     
         28 . The pharmaceutical composition of  claim 23 , wherein the isolated FRCs co-express CD140a and PD-L2. 
     
     
         29 . The pharmaceutical composition of  claim 23 , wherein the isolated FRCs co-express CD140a and LTBR. 
     
     
         30 . The pharmaceutical composition of  claim 23 , wherein the isolated FRCs co-express CD140a, PD-L2, and LTBR. 
     
     
         31 . The pharmaceutical composition of  claim 28 , wherein the isolated FRCs express at least one other lymphoid marker selected from the group consisting of PD-L1, Thy-1, MADCAM-1, MYH11, IL-7R, and ITGA7. 
     
     
         32 . The pharmaceutical composition of  claim 23 , wherein the isolated FRCs express at least one factor selected from the group consisting of IL-6, CCL19, CCL21, and VEGF. 
     
     
         33 . The pharmaceutical composition of  claim 23 , wherein the cells are isolated from a species selected from the group consisting of human, non-human primate, canine, feline, equine, swine, bovine, and rodent. 
     
     
         34 . The pharmaceutical composition of  claim 23 , wherein the cells suppress T cell proliferation in vitro. 
     
     
         35 . The pharmaceutical composition of  claim 23 , wherein the FRCs are isolated from lymph nodes, spleen, thymus, tonsils, adenoids, or Peyer's patches. 
     
     
         36 . The pharmaceutical composition of  claim 29 , wherein the isolated FRCs express at least one other lymphoid marker selected from the group consisting of PD-L1, Thy-1, MADCAM-1, MYH11, IL-7R, and ITGA7. 
     
     
         37 . The pharmaceutical composition of  claim 30 , wherein the isolated FRCs express at least one other lymphoid marker selected from the group consisting of PD-L1, Thy-1, MADCAM-1, MYH11, IL-7R, and ITGA7.