Composition for inducing proliferation or accumulation of regulatory t cells

Abstract

It was found that bacteria belonging to the genus Clostridium induce accumulation of regulatory T cells (Treg cells) in the colon. Moreover, the present inventors found that regulatory T cells (Treg cells) induced by from these bacteria suppressed proliferation of effector T-cells. From these findings, the present inventors found that the use of bacteria belonging to the genus Clostridium or a physiologically active substance derived therefrom made it possible to induce proliferation or accumulation of regulatory T cells (Treg cells), and further to suppress immune functions.

1 . A composition that induces proliferation or accumulation of regulatory T cells, the composition comprising, as an active ingredient, at least one substance selected from the group consisting of the following (a) to (c):
 (a) bacteria belonging to the genus  Clostridium  or a physiologically active substance derived from the bacteria;   (b) a spore-forming fraction of a fecal sample obtained from a mammal or a culture supernatant of the fraction; and   (c) a chloroform-treated fraction of a fecal sample obtained from a mammal or a culture supernatant of the fraction.   
     
     
         2 . The composition according to  claim 1 , wherein the regulatory T cells are transcription factor Foxp3-positive regulatory T cells or IL-10-producing regulatory T cells. 
     
     
         3 . The composition according to  claim 1 , wherein the composition has an immunosuppressive effect. 
     
     
         4 . The composition according to  claim 1 , wherein the composition is a pharmaceutical composition. 
     
     
         5 . A method for inducing proliferation or accumulation of regulatory T cells in an individual, the method comprising a step of administering, to the individual, at least one substance selected from the group consisting of the following (a) to (c):
 (a) bacteria belonging to the genus  Clostridium  or a physiologically active substance derived from the bacteria;   (b) a spore-forming fraction of a fecal sample obtained from a mammal or a culture supernatant of the fraction; and   (c) a chloroform-treated fraction of a fecal sample obtained from a mammal or a culture supernatant of the fraction.   
     
     
         6 - 7 . (canceled) 
     
     
         8 . The method according to  claim 5 , wherein a therapeutic composition is further administered to the individual. 
     
     
         9 . The method according to  claim 8 , wherein the therapeutic composition is at least one composition selected from the group consisting of corticosteroids, mesalazine, mesalamine, sulfasalazine, sulfasalazine derivatives, immunosuppressive drugs, cyclosporin A, mercaptopurine, azathiopurine, prednisone, methotrexate, antihistamines, glucocorticoids, epinephrine, theophylline, cromolyn sodium, anti-leukotrienes, anti-cholinergic drugs for rhinitis, anti-cholinergic decongestants, mast-cell stabilizers, monoclonal anti-IgE antibodies, vaccines, and combinations thereof. 
     
     
         10 . The method according to  claim 9 , wherein
 one measurement selected from the group consisting of promotion of IL-10 expression, promotion of CTLA4 expression, promotion of IDO expression, and suppression of IL-4 expression is used as an index of the induction of proliferation or accumulation of regulatory T cells in the individual.   
     
     
         11 - 12 . (canceled) 
     
     
         13 . A vaccine composition comprising at least one substance selected from the group consisting of the following (a) to (c):
 (a) bacteria belonging to the genus  Clostridium;      (b) a spore of bacteria in a spore-forming fraction of a fecal sample obtained from a mammal; and   (c) bacteria in a chloroform-treated fraction of a fecal sample obtained from a mammal.   
     
     
         14 . A method for treating, aiding in treating, reducing the severity of, or preventing at least one disease selected from infectious diseases and autoimmune diseases in an individual, the method comprising administering the vaccine composition according to  claim 13  to the individual. 
     
     
         15 - 17 . (canceled) 
     
     
         18 . A method of treatment comprising:
 (a) measuring the percentage and/or absolute amounts of  Clostridium  Clusters IV and XIV in the microbiota of a subject,   (b) comparing them to the same measurements in a healthy individual; and   (c) administering a substance to the subject, if a statistically significant decrease in the number/amounts of  Clostridium  cluster IV, XIV in the subject compared to the healthy individual is detected, wherein the substance is at least one substance selected from the group consisting of:   
       (i) a composition that induces proliferation or accumulation of regulatory T cells, the composition comprising, as an active ingredient, at least one substance selected from the group consisting of the following (a) to (c):
 (a) bacteria belonging to the genus  Clostridium  or a physiologically active substance derived from the bacteria; 
 (b) a spore-forming fraction of a fecal sample obtained from a mammal or a culture supernatant of the fraction; and 
 (c) a chloroform-treated fraction of a fecal sample obtained from a mammal or a culture supernatant of the fraction, 
 
       (ii) an antibiotic against Gram-negative bacteria; and 
       (iii) a vaccine composition comprising at least one substance selected from the group consisting of the following (a) to (c):
 (a) bacteria belonging to the genus  Clostridium;    
 (b) a spore of bacteria in a spore-forming fraction of a fecal sample obtained from a mammal; and 
 (c) bacteria in a chloroform-treated fraction of a fecal sample obtained from a mammal. 
 
     
     
         19 . (canceled)