Methods and compositions for modulating t cell and/or b cell activation

Abstract

The present invention provides methods of reducing or enhancing T cell activation and/or B cell activation in a subject, comprising administering to a subject an effective amount of an inhibitor or enhancer, respectively, of Semaphorin 6D (Sema6D) activity on T cells and/or B cells.

1 . A method of reducing T cell activation in a subject, comprising administering to a subject in need of reduced T cell activation an effective amount of an inhibitor of Semaphorin 6D (Sema6D) activity on T cells. 
     
     
         2 . The method of  claim 1 , wherein the subject is a transplantation patient, a subject having an autoimmune disease or at risk of having an autoimmune-disease (e.g., SLE, MS, RA, type I diabetes), and/or a subject having an inflammatory response or at risk of having an inflammatory response. 
     
     
         3 . The method of  claim 1 , wherein the inhibitor of Sema6D activity is an antibody that specifically binds Sema6D. 
     
     
         4 . The method of  claim 1 , wherein the inhibitor of Sema6D activity is administered in combination with another anti-T cell therapeutic, either simultaneously, before and/or after administration of the inhibitor of Sema6D activity. 
     
     
         5 . A method of increasing T cell activation in a subject, comprising administering to a subject in need of increased T cell activation an effective amount of an enhancer of Semaphorin 6D (Sema6D) activity on T cells. 
     
     
         6 . The method of  claim 5 , wherein the enhancer of Sema6D activity is administered in combination with another T cell activating therapeutic, either simultaneously, before and/or after administration of the enhancer of Sema6D activity. 
     
     
         7 . A method of identifying an activated T cell, comprising detecting Sema6D on the surface of the T cell. 
     
     
         8 . A method of identifying an activated T cell, comprising detecting messenger RNA encoding Sema6D in the T cell. 
     
     
         9 . A method of monitoring T cell activation over time, comprising detecting Sema6D on the surface of a T cell over time and measuring changes in the amount of Sema6D on the surface of a T cell over time. 
     
     
         10 . A method of monitoring T cell activation over time, comprising detecting messenger RNA encoding. Sema6D in a T cell over time and measuring changes in the amount of messenger RNA encoding Sema6D in the T cell over time. 
     
     
         11 . A method of identifying a substance having an inhibitory effect on Sema6D activity and/or having an inhibitory effect on T cell activation, comprising contacting the substance with T cells under conditions whereby Sema6D activity and/or T cell activation can occur and measuring the amount of Sema6D activity and/or T cell activation in the presence and in the absence of the substance; whereby a decrease in Sema6D activity and/or T cell activation in the presence of the substance as compared to the amount of Sema6D activity and or/T cell activation in the absence of the substance identifies a substance having the ability to inhibit Sema6D activity and/or T cell activation. 
     
     
         12 . A method of identifying a substance having an enhancing effect on Sema6D activity and/or T cell activation, comprising contacting the substance with T cells under conditions whereby Sema6D activity and/or T cell activation can occur and measuring the amount of Sema6D activity and/or T cell activation in the presence and in the absence of the substance; whereby an increase in Sema6D activity and/or T cell activation in the presence of the substance as compared to the amount of Sema6D activity and/or T cell activation in the absence of the substance identifies a substance having the ability to enhance Sema6D activity and/or T cell activation. 
     
     
         13 . A method of reducing B cell activation in a subject, comprising administering to a subject in need of reduced B cell activation an effective amount of an inhibitor of Semaphorin 6D (Sema6D) activity on B cells. 
     
     
         14 . The method of  claim 13 , wherein the subject is a transplantation patient, a subject having an autoimmune disease or at risk of having an autoimmune disease (e.g., SLE, MS, RA, type I diabetes), and/or a subject having an inflammatory response or at risk of having an inflammatory response. 
     
     
         15 . The method of  claim 13 , wherein the inhibitor of Sema6D activity is an antibody that specifically binds Sema6D. 
     
     
         16 . The method of  claim 13 , wherein the inhibitor of Sema6D activity is administered in combination with another anti-B cell therapeutic, either simultaneously, before and/or after administration of the inhibitor of Sema6D activity. 
     
     
         17 . A method of increasing B cell activation in a subject, comprising administering to a subject in need of increased B cell activation an effective amount of an enhancer of Semaphorin 6D (Sema6D) activity on B cells. 
     
     
         18 . The method of  claim 17 , wherein the enhancer of Sema6D activity is administered in combination with another B cell activating therapeutic, either simultaneously, before and/or after administration of the enhancer of Sema6D activity. 
     
     
         19 . A method of identifying an activated B cell, comprising detecting Sema6D on the surface of the B cell. 
     
     
         20 . A method of identifying an activated B cell, comprising detecting messenger RNA encoding Sema6D in the B cell. 
     
     
         21 . A method of monitoring B cell activation over time, comprising detecting Sema6D on the surface of a B cell over time and measuring changes in the amount of Sema6D on the surface of a B cell over time. 
     
     
         22 . A method of monitoring B cell activation over time, comprising detecting messenger RNA encoding Sema6D in a B cell over time and measuring changes in the amount of messenger RNA encoding Sema6D in the B cell over time. 
     
     
         23 . A method of identifying a substance having an inhibitory effect on Sema6D activity and/or having an inhibitory effect on B cell activation, comprising contacting the substance with B cells under conditions whereby Sema6D activity and/or B cell activation can occur and measuring the amount of Sema6D activity and/or B cell activation in the presence and in the absence of the substance; whereby a decrease in Sema6D activity and/or B cell activation in the presence of the substance as compared to the amount of Sema6D activity and or/B cell activation in the absence of the substance identifies a substance having the ability to inhibit Sema6D activity and/or B cell activation. 
     
     
         24 . A method of identifying a substance having an enhancing effect on Sema6D activity and/or B cell activation, comprising contacting the substance with B cells under conditions whereby Sema6D activity and/or B cell activation can occur and measuring the amount of Sema6D activity and/or B cell activation in the presence and in the absence of the substance; whereby an increase in Sema6D activity and/or B cell activation in the presence of the substance as compared to the amount of Sema6D activity and/or B cell activation in the absence of the substance identifies a substance having the ability to enhance Sema6D activity and/or B cell activation. 
     
     
         25 . A method of treating a B cell-related disorder in a subject, comprising administering to the subject a therapeutic amount of an inhibitor of Semaphorin 6D (Sema6D) activity on B cells. 
     
     
         26 . The method of  claim 25 , wherein the disorder is selected from the group consisting of leukemia, lymphoma, an autoimmune disorder, inflammatory response, transplantation rejection and any combination thereof. 
     
     
         27 . A method of treating a T cell-related disorder in a subject, comprising administering to the subject a therapeutic amount of an inhibitor of Semaphorin 6D (Sema6D) activity on B cells. 
     
     
         28 . The method of  claim 27 , wherein the disorder is selected from the group consisting of leukemia, lymphoma, autoimmune disease, inflammatory response, transplantation rejection and any combination thereof. 
     
     
         29 . A method of treating a white blood cell-related disorder in a subject, comprising administering to the subject a therapeutic amount of an inhibitor of Semaphorin 6D (Sema6D) activity on white blood cells. 
     
     
         30 . The method of  claim 29 , wherein the disorder is selected from the group consisting of leukemia (e.g., chronic myelogenous leukemia; promyelocytic leukemia), lymphoma, an autoimmune disorder and any combination thereof.