Effect of house dust mite immunotherapy on transforming growth factor beta1-producing T cells in asthmatic children.
BACKGROUND
Recent evidence suggests that regulatory T cells (Treg cells) and immunosuppressive cytokines, such as transforming growth factor BETA1 (TGF-BETA1) and interleukin 10 (IL-10), may have a role in clinically effective allergen specific immunotherapy (SIT).


OBJECTIVE
To evaluate the effect of SIT on the induction of Treg cells in house dust mite-allergic children and on the expression of specific Treg cell markers (cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], IL-10, and TGF-BETA1).


METHODS
In this uncontrolled open-label study, the percentage of peripheral blood CD4+ Treg cells (CD69 CD45RO+CTLA-4+ and CD3+CD4+CD25+FOXP3+) and the expression of molecules associated with their functions (CTLA-4, TGF-BETA1, and IL-10) were analyzed using flow cytometry in 16 children allergic to house dust mites before and at 3 and 12 months of subcutaneous SIT. Clinical variables, such as symptom score, medication requirements, forced expiratory volume in 1 second, peak expiratory flow rate, and serum IgE levels, were also determined. Ten healthy children were included as controls.


RESULTS
All the clinical variables improved during immunotherapy. The percentage of CD4+CD25+CD69-CD45RO+ Treg cells remained unchanged. The percentage of CTLA-4+ -expressing Treg cells transiently increased after 3 months of immunotherapy, whereas the percentage of FOXP3+ Treg cells did not change after 1 year of immunotherapy. Levels of IL-10+ cells transiently decreased after 3 months of immunotherapy. Four children who required inhaled fluticasone propionate administration for significant symptom worsening had no statistically significant increase in TGF-BETA1-secreting T cells at 12 months of SIT, in contrast to 12 children without inhaled corticosteroid treatment.


CONCLUSIONS
The increase in TGF-BETA1-positive T cells only in children without significant symptom worsening requiring inhaled corticosteroid treatment limits the usefulness of TGF-BETA1 in monitoring response to allergen immunotherapy.
Ajduk
Jakov
J
Institute of Immunology, Zagreb, Croatia.
Marinic
Igor
I
Aberle
Neda
N
Rabatic
Sabina
S
Gagro
Alenka
A
D000818:Animals; D015703:Antigens, CD / Q000097:blood / Q000276:immunology; D039741:Antigens, Dermatophagoides / Q000627:therapeutic use*; D000943:Antigens, Differentiation / Q000097:blood / Q000276:immunology; D060829:Arthropod Proteins; D001249:Asthma / Q000276:immunology* / Q000628:therapy; D060908:CTLA-4 Antigen; D002648:Child; D002675:Child, Preschool; D003546:Cysteine Endopeptidases; D005260:Female; D005434:Flow Cytometry; D005541:Forced Expiratory Volume / Q000187:drug effects / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D007167:Immunotherapy / Q000379:methods*; D016753:Interleukin-10 / Q000097:blood / Q000276:immunology; D008297:Male; D010366:Peak Expiratory Flow Rate / Q000187:drug effects / Q000276:immunology; D039981:Pyroglyphidae / Q000276:immunology*; D018709:Statistics, Nonparametric; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D053773:Transforming Growth Factor beta1 / Q000097:blood / Q000276:immunology*
D015703:Antigens, CD; D039741:Antigens, Dermatophagoides; D000943:Antigens, Differentiation; D060829:Arthropod Proteins; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D053773:Transforming Growth Factor beta1; D016753:Interleukin-10; D003546:Cysteine Endopeptidases; C451162:Dermatophagoides pteronyssinus antigen p 1