Cellular populations and uses thereof

Abstract

Disclosed are methods of identifying immunosuppressive T R 1 regulatory T cells, including methods of diagnosing the presence of immune tolerance, methods of producing immunosuppressive regulatory T cells, and methods of eliciting immune tolerance in a subject. These methods include screening T cells to detect Eomes + IL-10 + T cells or expressing recombinant Eomes in T cell populations to generate immunosuppressive regulatory T cells.

1 - 67 . (canceled) 
     
     
         68 . A method of identifying immunosuppressive TR1 regulatory T cells in a sample, the method comprising: screening T cells in the sample for Eomes+IL− 10 +CD4+T cells, detecting Eomes+IL− 10 +CD4+T cells; and identifying the detected T-cells as immunosuppressive TR 1  regulatory T cells. 
     
     
         69 . The method of  claim 68 , further comprising isolating the identified immunosuppressive regulatory T-cells. 
     
     
         70 . The method of  claim 68 , wherein the screening of the T cells in the sample comprises detecting Eomeshi CD4+T cells. 
     
     
         71 . The method of  claim 68 , wherein the screening of the T cells in the sample comprises detecting Eomes+IL−10hi CD4+T cells. 
     
     
         72 . The method of  claim 68 , wherein the screening of the T cells in the sample comprises detecting EomeshiIL−10hi CD4+T cells. 
     
     
         73 . The method of  claim 68 , wherein the screening of the T cells in the sample comprises detecting T-betloEomes+IL−10+CD4+T cells. 
     
     
         74 . The method of  claim 68 , wherein the screening of the T cells in the sample comprises detecting Eomes+IL−10+CD4+T cells that are positive or high for IFN□. 
     
     
         75 . The method of  claim 68 , wherein the screening of the T cells in the sample comprises detecting Eomes+IL− 10 +CD4+T cells that are positive for at least one of CD122, α4β7, LAG-3, Ly6C and TIGIT. 
     
     
         76 . The method of  claim 68 , wherein the screening of the T cells in the sample comprises detecting Eomes+IL−10+CD4+T cells that are negative or low for one or more of CD25, CD69 and FoxP3. 
     
     
         77 . The method of  claim 68 , wherein the screening of the T cells in the sample comprises detecting Eomes+IL−10+CD4+T cells that are positive for at least one of CD122, α4β7, LAG-3, Ly6C and TIGIT, and that are negative or low for one or more of CD25, CD69 and FoxP3. 
     
     
         78 . The method of  claim 68 , wherein the screening of the T cells in the sample comprises detecting Eomes+IL−10+CD4+ T cells that are negative or low for at least one TH2 cytokine. 
     
     
         79 . The method of  claim 78 , wherein the at least one TH2 cytokine is selected from the group consisting of IL-4, IL-13 and IL-5. 
     
     
         80 . The method of  claim 68 , wherein the screening of the T cells in the sample comprises detecting Eomes+IL−10+CD4+T cells that are negative or low for at least one TH17 cytokine. 
     
     
         81 . The method of  claim 80 , wherein the at least one TH17 cytokine is selected from the group consisting of IL-17, IL-6 and GM-CSF. 
     
     
         82 . The method of  claim 68 , further comprising detecting suppression by the Eomes+IL−10+CD4+T cells of at least one immune function selected from the group consisting of IL-2 production, cell proliferation, cytokine production, cell migration, and effector functions, killing, and T-cell proliferation. 
     
     
         83 . The method of  claim 68 , wherein the sample is a peripheral blood mononuclear cell sample. 
     
     
         84 . The method of  claim 68 , wherein the sample is a lymphoid tissue sample.