Compositions and methods for modulating an immune response

Abstract

The invention provides methods of modulating follicular regulatory T (TFR) cell-mediated immune responses and the use of those methods in the treatment of diseases or conditions such as viral, bacterial, pathogenic, or fungal infections or cancer. Such methods provide for boosting of antibody production through the use of IL-21 to overcome TFR cell suppression of antibody production.

1 - 35 . (canceled) 
     
     
         36 . A method of reducing immune suppressive activity of TFR cells in adoptive immunotherapy, comprising contacting TFR cells isolated from a subject with a cytokine in-vitro or ex-vivo, and wherein the reduced immune suppressive activity results in a protective antibody response, wherein the cytokine is IL-21 or IL-6. 
     
     
         37 . The method of  claim 36 , wherein the reduced immune suppressive activity is characterized by a boost of antibody production as compared to native TFR cells. 
     
     
         38 . The method of  claim 36 , wherein the method comprises contacting the TFR cells isolated from a subject with IL-21. 
     
     
         39 . The method of  claim 36 , wherein the method comprises contacting the TFR cells isolated from a subject with IL-6. 
     
     
         40 . A composition comprising TFR cells, TFH cells, and a cytokine, wherein said composition has reduced immune suppressive activity,
 wherein the reduced immune suppressive activity results in a protective antibody response, and   wherein the cytokine is IL-21 or IL-6.   
     
     
         41 . The composition of  claim 40 , wherein the cytokine is IL-21. 
     
     
         42 . The composition of  claim 40 , wherein the cytokine is IL-6. 
     
     
         43 . A vaccine composition comprising the composition of  claim 40 . 
     
     
         44 . A method of treating an allergy in a subject, the method comprising administering the composition of  claim 40 . 
     
     
         45 . An adjuvant comprising a composition of TFH cells and a cytokine, wherein the TFH cells have an enhanced stimulatory capacity, and wherein the cytokine is IL-21 or IL-6. 
     
     
         46 . The adjuvant of  claim 45 , wherein the enhanced stimulatory capacity results in an increase in antibody production. 
     
     
         47 . The adjuvant of  claim 45 , wherein the cytokine is IL-21. 
     
     
         48 . The adjuvant of  claim 45 , wherein the cytokine is IL-6. 
     
     
         49 . The adjuvant of  claim 45 , wherein the TFH cells are purified from the peripheral blood of a subject. 
     
     
         50 . A method of boosting the antibody production in a subject in need thereof by administering the adjuvant of  claim 45  to the subject.