Regulation of cytokine production in T-cell responses to inhalant allergen: GATA-3 expression distinguishes between Th1-and Th2-polarized immunity

Background: The precise nature of allergen-specific cytokine responses in a topics versus non-atopics, in particular the 'Th1 polarity' of responses in non-atopics, remains controversial. This is due in part to the relative in sensitivity of cytokine detection systems, and associated variations in kin etics of cytokine production and catabolism in in vitro culture systems. As an alternative to cytokine measurement, this study focuses on expression o f the transcription factor GATA-3 for analysis of allergen-specific Th cell responses. Methods: Cord blood mononuclear cells were Th1- or Th2-polarize d by cu Itu re in IL-12- or IL-4-employing established methods; PBMC from h ouse dust mite (HDM)-sensitive atopics and controls were stimulated overnig ht with HDM; cytokine production was measured by ELISA and GATA-3 mRNA expr ession by PCR. Results: Cytokine-driven Th2 polarization of naive T cells i s associated with marked upregulation of GATA-3 expression, whereas a recip rocal expression pattern accompanies differentiation towards the Th1 cytoki ne phenotype. In T cells from HDM skin prick test-positive (HDM-SPT+/HDM-Ig E+) volunteers, overnight stimulation results in marked upregulation of GAT A-3 expression, compared to an equally marked downregulation of expression in T cells from SPT-/IgE-subjects. In subjects who are HDM-SPT+ but IgE-, G ATA-3 expression levels remained relatively stable during culture with HDM. Conclusions: Upregulation of GATA-3 expression in PBMC is a hallmark of th e early phase of Th2 recall responses to specific allergen in atopics. The reciprocal expression pattern observed in HDM-specific recall responses of non-atopics provides independent confirmation of the presence of underlying Th1-like immunity in these subjects. The parallel findings in neonatal T c ells suggest that the same approach may be utilized for monitoring the prog ress of allergen-specific Th1/Th2 memory development during early childhood , and hence in assessment of risk for future allergic disease. Copyright (C ) 2001 S. Karger AG, Basel.