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.
Bohle
Barbara
B
Department of Pathophysiology, Center for Physiology, Pathophysiology, and Immunology, Medical University of Vienna, Vienna, Austria. barbara.bohle@meduniwien.ac.at
Kinaciyan
Tamar
T
Gerstmayr
Marianne
M
Radakovics
Astrid
A
Jahn-Schmid
Beatrice
B
Ebner
Christof
C
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