Effects of subcutaneous immunotherapy (SCIT) on the numbers of IL-10-producing CD4+ T cells and IL-10-producing B cells in peripheral blood of pollinosis patients

RATIONALE: It has been suggested that mechanisms underlying effectiveness of antigen-specific immunotherapy are related to increases in IgG4 antibody and regulatory T and B cells, whereas their precise roles have been unclear.

METHODS: After the pollen season in 2017, peripheral blood was drawn from normal subjects, Japanese cedar plollinosis patients and patients treated with SCIT for more than 3 years. Peripheral blood mononuclear cells (PBMC) were collected by a density gradient method, and stimulated with the specific antigen, Cry j 1 or anti-CD3/CD28 mAb. Then, cell surface molecules and intracellular IL-10 and Foxp3 were stained, followed by flowcytometer analyses.

RESULTS: 1) Although increase in antigen-specific IgE antibody level was not statistically reduced by SCIT, antigen-specific IgG4 level was dramatically increased in the SCIT-treated patients. 2) The number of antigen-induced IL-10-producing CD4⁺ T cells in PBMC of the pollenosis patients was significantly lower than that of the normal subjects. However, the number of antigen-induced IL-10-producing CD4⁺ T cells of the SCIT-treated pollenosis patients was comparable to that of the normal subjects. Most of the IL-10-producing CD4⁺ T cells were negative for Foxp3, a transcription factor of naturally occurring regulatory T cells. 3) The number of IL-10-producing B cells of the pollenosis patients was not different from that of normal subjects, whereas that of SCIT-treated patients was significantly higher than those of other 2 groups.

CONCLUSIONS: Regulatory functions of the IL-10-producing CD4⁺ Foxp3^- T cells and IL-10-producing B cells could be involved in mechanisms underlying the clinical effects of SCIT.