Sublingual immunotherapy induces IL-10-producing T regulatory cells, allergen-specific T-cell tolerance, and immune deviation.
BACKGROUND
The immunologic mechanisms underlying sublingual immunotherapy (SLIT) are still unclear, particularly the role of regulatory T cells.


OBJECTIVE
We sought to characterize allergen-specific T-cell responses during successful birch pollen SLIT.


METHODS
Proliferation of PBMCs and PBMCs depleted of CD25(+) cells obtained from 9 patients before, after 4 weeks, and after 52 weeks of SLIT was assessed in response to the major birch pollen allergen Bet v 1, the homologous apple allergen Mal d 1, or tetanus toxoid. Allergen-induced cytokine responses and FoxP3 expression of T cells were analyzed by using real-time PCR. The role of IL-10 for regulatory activity of T cells was investigated.


RESULTS
After 4 weeks, higher frequencies of circulating CD4(+)CD25(+) T cells were detected together with increased FoxP3 and IL-10 and reduced IL-4 and IFN-gamma mRNA expression levels compared with those before SLIT. Proliferation to all 3 antigens was markedly reduced but increased significantly after depletion of CD25(+) cells or addition of anti-IL-10 antibodies. After 52 weeks, proliferation in response to Mal d 1 or tetanus toxoid returned to pre-SLIT levels, whereas Bet v 1-induced proliferation remained significantly suppressed and was enhanced by neither depletion of CD25(+) cells nor addition of anti-IL-10 antibodies. In parallel, increased IFN-gamma and reduced IL-4, IL-10, and FoxP3 mRNA expression was detected. Neither TGF-beta levels nor cell-cell contact-mediated suppression of CD4(+)CD25(+) cells changed during the course of SLIT.


CONCLUSIONS
SLIT induces regulatory T-cell suppression through IL-10 during the early phase and specific nonreactivity and immune deviation of allergen-specific T cells during the later phase of therapy.


CONCLUSIONS
SLIT induces immune mechanisms comparable with subcutaneous specific immunotherapy.
Department of Pathophysiology, Center for Physiology, Pathophysiology, and Immunology, Medical University of Vienna, Vienna, Austria. barbara.bohle@meduniwien.ac.at
Barbara
B
Bohle
Tamar
T
Kinaciyan
Marianne
M
Gerstmayr
Astrid
A
Radakovics
Beatrice
B
Jahn-Schmid
Christof
C
Ebner
D000286:Administration, Sublingual; D000485:Allergens / Q000008:administration & dosage* / Q000276:immunology; D029662:Betula / Q000276:immunology; D049109:Cell Proliferation; D003888:Desensitization, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000276:immunology; D006801:Humans; D006967:Hypersensitivity / Q000517:prevention & control*; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology; D008137:Longitudinal Studies; D011058:Pollen / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000485:Allergens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma