T cell balance gene expression, compositions of matters and methods of use thereof

Abstract

This invention relates generally to compositions and methods for identifying the regulatory network that modulates, controls or otherwise influences T cell balance, for example, Th17 cell differentiation, maintenance and/or function, as well compositions and methods for exploiting the regulatory network that modulates, controls or otherwise influences T cell balance in a variety of therapeutic and/or diagnostic indications. This invention also relates generally to identifying and exploiting target genes and/or target gene products that modulate, control or otherwise influence T cell balance in a variety of therapeutic and/or diagnostic indications.

1 . A method of diagnosing, prognosing and/or staging an immune response involving T cell balance, comprising detecting a first level of expression, activity and/or function of CD5L and comparing the detected level to a control of level of CD5L expression, activity and/or function, wherein a difference in the detected level and the control level indicates that the presence of an immune response in the subject. 
     
     
         2 . The method of  claim 1 , wherein an immune response is monitored in a subject comprising detecting a level of expression, activity and/or function of CD5L at a first time point, detecting a level of expression, activity and/or function of CD5L at a second time point, and comparing the first detected level of expression, activity and/or function with the second detected level of expression, activity and/or function, wherein a change in the first and second detected levels indicates a change in the immune response in the subject. 
     
     
         3 . The method of  claim 1 , wherein a patient population at risk or suffering from an immune response is identified comprising detecting a level of expression, activity and/or function of CD5L in the patient population and comparing the level of expression, activity and/or function of CD5L in a patient population not at risk or suffering from an immune response, wherein a difference in the level of expression, activity and/or function of CD5L in the patient populations identifies the patient population as at risk or suffering from an immune response. 
     
     
         4 . A method for monitoring subjects undergoing a treatment or therapy for an aberrant immune response to determine whether the patient is responsive to the treatment or therapy comprising detecting a level of expression, activity and/or function of IL17A in the absence of the treatment or therapy and comparing the level of expression, activity and/or function of IL17A in the presence of the treatment or therapy, wherein a difference in the level of expression, activity and/or function of IL17A in the presence of the treatment or therapy indicates whether the patient is responsive to the treatment or therapy, wherein the treatment or therapy is specific for CD5L. 
     
     
         5 . The method of  claim 1 , wherein the immune response is an autoimmune response or an inflammatory response. 
     
     
         6 . The method of  claim 5  wherein the inflammatory response is associated with an autoimmune response, an infectious disease and/or a pathogen-based disorder. 
     
     
         7 . The method of  claim 4 , wherein the treatment or therapy is an antagonist of CD5L in an amount sufficient to switch Th17 cells from a non-pathogenic to pathogenic signature; or wherein the treatment or therapy is an agonist that enhances or increases the expression of CD5L in an amount sufficient to switch Th17 cells from a pathogenic to a non-pathogenic signature. 
     
     
         8 . The method according to  claim 7 , wherein the treatment or therapy targets T cells and the T cells are naïve T cells, partially differentiated T cells, differentiated T cells, a combination of naïve T cells and partially differentiated T cells, a combination of naïve T cells and differentiated T cells, a combination of partially differentiated T cells and differentiated T cells, or a combination of naïve T cells, partially differentiated T cells and differentiated T cells. 
     
     
         9 . A method of modulating T cell balance, the method comprising contacting a Th17 cell or a population of T cells comprising Th17 cells or T cells capable of differentiating into Th17 cells with an exogenous T cell modulating agent in an amount sufficient to modify maintenance and/or function of the Th17 cell or population of T cells by altering balance between pathogenic and non-pathogenic Th17 cells as compared to maintenance and/or function of the Th17 cell or population of T cells in the absence of the T cell modulating agent, wherein the T cell modulating agent is specific for CD5L. 
     
     
         10 . The method of  claim 9 , wherein the T cell modulating agent is an antagonist of CD5L in an amount sufficient to switch Th17 cells from a non-pathogenic to pathogenic signature. 
     
     
         11 . The method of  claim 9 , wherein the T cell modulating agent is an agonist that enhances or increases the expression of CD5L in an amount sufficient to switch Th17 cells from a pathogenic to non-pathogenic signature. 
     
     
         12 . The method according to  claim 9 , wherein the population of T cells comprise naïve T cells, partially differentiated T cells, differentiated T cells, a combination of naïve T cells and partially differentiated T cells, a combination of naïve T cells and differentiated T cells, a combination of partially differentiated T cells and differentiated T cells, or a combination of naïve T cells, partially differentiated T cells and differentiated T cells. 
     
     
         13 . A method of drug discovery for the treatment of a disease or condition involving an immune response involving Th17 cells comprising the steps of:
 (a) providing a population of cells or tissue comprising Th17 cells;   (b) providing a CD5L specific compound or plurality of compounds to be screened for their efficacy in the treatment of said disease or condition;   (c) contacting said compound or plurality of compounds with said population of cells or tissue;   (d) detecting a first level of expression, activity and/or function of one or more signature genes or one or more products of one or more signature genes selected from the genes of Table 1 or Table 2;   (e) comparing the detected level to a control of level of one or more signature genes or one or more products of one or more signature genes selected from the genes of Table 1 or Table 2 or gene product expression, activity and/or function; and,   (e) evaluating the difference between the detected level and the control level to determine the immune response elicited by said CD5L specific compound or plurality of compounds.