Human leukocyte antigen-G and regulatory T cells during specific immunotherapy for pollen allergy

Background: T_H2-biased immune responses are important in allergy pathogenesis. Mechanisms of allergen-specific immunotherapy (SIT) might include the induction of regulatory T cells (Tregs) and immunoglobulin (Ig) G₄ blocking antibodies, a reduction in the number of effector cells, and skewing of the cytokine profile towards a T_H1-polarized immune response. We investigated the effects of SIT on T cells, on immunomodulation of human leukocyte antigen (HLA)-G, which has been associated with allergy, on regulatory cytokine expression, and on serum allergen-specific antibody subclasses (IgE and IgG₄). Methods: Eleven birch and/or grass pollen-allergic patients and 10 healthy nonatopic controls were studied before and during SIT. Tregs, chemokine receptors, soluble HLA-G (sHLA-G), Ig-like transcript (ILT) 2, specific IgE, and IgG₄ were studied. Peripheral blood mononuclear cells (PBMCs) were stimulated with pollen extract in vitro and immune factors were evaluated. Results: During SIT, the main changes in the peripheral blood were an increase in CXCR3⁺CD4⁺CD25⁺CD127^low/- Tregs and a decrease in CCR4⁺CD4⁺CD25⁺CD127^low/- Tregs, an increase in allergen-specific IgG₄, and a decrease in sHLA-G during the first half of the treatment period. In the PBMC in vitro experiments, the following changes were observed upon allergen-stimulation: an increase in CD4⁺CD25⁺CD127^low/- Tregs and ILT2⁺CD4⁺CD25⁺CD127^low/- Tregs, an increase in IL-10 and IL-2 levels, and an increase in sHLA-G that was most pronounced at the start of SIT. Conclusions: The changes in CXCR3⁺CD4⁺CD25⁺CD127^low/- Treg, IgG₄, and sHLA-G levels in the peripheral blood and in ILT2⁺ Treg, IL-10, IL-2, and sHLA-G levels upon in vitro allergen stimulation suggest an upregulation in immunomodulatory factors and, to some degree, a shift towards T_H1 during SIT.