Understanding the immunological basis of asthma; immunotherapy and regulatory T cells.
We believe that immunotherapy with HKL as an adjuvant induces Thl-like TReg cells that can inhibit AHR and airway inflammation. These antigen-specific TReg cells are induced with CD8alpha+ DCs producing IL-12 and IL-10, produce IFN-gamma and IL-10, and also express T-bet and Foxp3. These Th1Reg cells are distinct from antigen-specific TReg cells induced with respiratory tolerance, which can also inhibit AHR and airway inflammation. These Th2-like TReg cells are induced with CD8alpha- DCs producing IL-10, they express IL-10, GATA3 and Foxp3. So allergen immunotherapy is effective in large part because it induces regulatory T cells. With HKL you get Th1Reg cells, and with other forms of immunotherapy you may get Th2Reg cells. We believe that with further refinements, allergen immunotherapy that rapidly induces allergen specific TReg cells will indeed be the magic bullets for allergy and asthma.
Umetsu
Dale T
DT
Division of Immunology, Karp Lab, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA.
D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000628:therapy*; D003888:Desensitization, Immunologic; D050990:GATA3 Transcription Factor / Q000032:analysis; D006801:Humans; D051379:Mice; D010047:Ovalbumin / Q000276:immunology; D020825:T-Box Domain Proteins / Q000032:analysis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D000098815:T-bet Transcription Factor
D050990:GATA3 Transcription Factor; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D010047:Ovalbumin