Abstract
The role of adaptive immune system in regulation of asthmatic responses remains elusive. Here, we performed a comprehensive time-course analysis of mutual relationships between development of asthmatic response following allergen challenge and changes in several CD4+ T cell subsets which we characterized as either releasing interleukin-10 (CD4+CD25−CD127− and CD4+CD25+CD127+ T cells) or responding to IL-10 (CD4+ T cell subsets expressing CD210). Patients that developed asthmatic reaction were described as responders (R) whereas the others were named non-responders (NR). In R, in contrast to NR, at 6 h, we demonstrated significant expansion of CD4+CD25−CD127− T cells which was followed by drop to baseline values at 24 h. In contrast, in R, we observed decrease in numbers of CD4+CD25+CD127+ and CD4+CD25−CD127+ T cells at 24 h. Interestingly, at baseline, despite comparable IL-10 levels, R presented with lower levels of all CD4+ T cell subsets expressing CD210. In R, the numbers of CD4+CD210+ T cell subsets were further decreased following bronchial challenge which was paralleled by decrease in IL-10 serum levels. Altogether, our data suggest that dynamic interactions between IL-10-producing and IL-10-responding CD4+ T cells could contribute to pathogenesis of asthmatic responses in atopic individuals.
Highlights
CD4+ T cells play crucial roles in regulation of immune responses underlying allergic inflammation [1]
We presented here a novel pattern of dynamic interactions between CD4+ T cell subsets capable of producing IL-10 and those that could respond to its actions mediated by IL-10R
Assessment of CD25 and CD127 expression serves as a sensitive marker for delineation of natural regulatory T cells characterized by CD4+CD25+CD127− phenotype
Summary
CD4+ T cells play crucial roles in regulation of immune responses underlying allergic inflammation [1]. Enhancement of IL-10 production by peripheral CD4+ T cells in patients developing asthmatic response upon bronchial allergen challenge was demonstrated by Matsumoto et al [4]. The use of combination of anti-CD25 and anti-CD127 antibodies has allowed for precise delineation of natural Treg cells (characterized by CD4+CD25+CD127− phenotype with high expression of FoxP3), and putative adaptive Treg cells, namely CD4+CD25−CD127− T cells. This subset was demonstrated to possess suppressive features despite the absence of CD25 expression and low expression of FoxP3 [5,6,7]. Dynamic changes in distribution of CD4+ T cells with nonregulatory phenotype (mostly positive for CD127) were not analyzed in the context of development of asthmatic responses in sensitive subjects exposed to specific allergen
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