Method for detecting regulatory t cells using expression of folate receptor 4 as indicator, method for treating diseases using the detection method, pharmaceutical composition for immunostimulation, and method for treating diseases using the compostion

Abstract

An object of the present invention is to provide a technique to distinguish between T reg cells and activated T cells in a live state. Another object of the present invention is to provide a pharmaceutical composition for immunostimulation that can reduce the number of T reg cells in vivo and effectively express the immune response of activated T cells. In the method of the present invention, T reg cells are detected from test cells containing (i) regulatory T cells and (ii) at least one type of cell selected from the group consisting of naive T cells and activated T cells, wherein expressions of folate receptor 4 on the surfaces of cells are measured and T reg cells are detected using the expressions as an indicator. The present invention uses anti-folate receptor 4 antibody or folate receptor 4-binding fragment as an active ingredient contained in a pharmaceutical composition for immunostimulation.

1 . A method for detecting regulatory T cells from test cells containing (i) regulatory T cells and (ii) at least one type of cell selected from the group consisting of naive T cells and activated T cells,
 the method comprising the steps of measuring expressions of folate receptor 4 on the surfaces of the test cells and detecting regulatory T cells using the expressions as an indicator.   
   
   
       2 . A detection method according to  claim 1 , wherein the expressions of folate receptor 4 are measured using anti-folate receptor 4 antibody or folate receptor 4-binding fragment. 
   
   
       3 . A method for isolating regulatory T cells comprising the step of isolating cells contained in a cell group having the most intensive folate receptor 4 expressions from test cells containing (i) regulatory T cells, and (ii) at least one type of cell selected from the group consisting of naive T cells and activated T cells. 
   
   
       4 . An isolation method according to  claim 3 , wherein the test cells are those comprising T cells isolated from a mammal or comprising cells obtained by subjecting naive T cells to antigenic stimulus. 
   
   
       5 . (canceled) 
   
   
       6 . A method for suppressing immunity after organ transplant comprising:
 step (a) collecting cells containing T cells from a patient received an organ transplant;   step (b) obtaining regulatory T cells by isolating cells contained in a cell group having the most intensive folate receptor 4 expressions from the cells obtained in the step (a) or cells in which regulatory T cells were induced by subjecting the cells obtained in the step (a) to antigenic stimulus; and   step (c) administering regulatory T cells obtained in the step (b) to the patient.   
   
   
       7 . A method for treating autoimmune diseases comprising:
 step (a) collecting cells containing T cells from a patient suffering from an autoimmune disease;   step (b) obtaining regulatory T cells by isolating cells contained in a cell group having the most intensive folate receptor 4 expressions from the cells obtained in the step (a) or cells in which regulatory T cells were induced by subjecting the cells obtained in the step (a) to antigenic stimulus; and   step (c) administering regulatory T cells obtained in the step (b) to the patient.   
   
   
       8 . A reagent for detecting regulatory T cells comprising anti-folate receptor 4 antibody or folate receptor 4-binding fragment. 
   
   
       9 . A pharmaceutical composition for immunostimulation comprising anti-folate receptor 4 antibody or folate receptor 4-binding fragment. 
   
   
       10 . An pharmaceutical composition for treating tumors comprising anti-folate receptor 4 antibody or folate receptor 4-binding fragment. 
   
   
       11 . An immunostimulation method comprising the step of administering an amount of anti-folate receptor 4 antibody or folate receptor 4-binding fragment effective for activating immunity to a mammal including human. 
   
   
       12 . A method for treating a patient suffering from a malignant tumor or infectious disease comprising the step of administering an amount of anti-folate receptor 4 antibody or folate receptor 4-binding fragment effective for treating malignant tumor to the patient.