Enforced expression of GATA-3 in transgenic mice inhibits Th1 differentiation and induces the formation of a T1/ST2-expressing Th2-committed T cell compartment in vivo

MC Nawijn, GM Dingjan, R Ferreira, BN Lambrecht, A Karis, F Grosveld, H Savelkoul, RW Hendriks*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

78 Citations (Scopus)

Abstract

The transcription factor GATA-3 is essential for early T cell development and differentiation of naive CD4(+) T cells into Th2 effector calls. To study the function of GATA-3 during T cell-mediated immune responses in vivo, we investigated CD2-GATA3-transgenic mice in which GATA-3 expression is driven by the CD2 locus control region. Both in the CD4(+) and the CD8(+) T cell population the proportion of cells exhibiting a CD44(high)CD45RB(low)CD62L(low) Ag-experienced phenotype was increased. In CD2-GATA3-transgenic mice, large fractions of peripheral CD4(+) T cells expressed the IL-1 receptor family member T1/ST2, indicative of advanced Th2 commitment. Upon in vitro T call stimulation, the ability to produce IL-2 and IFN-gamma was decreased. Moreover, CD4(+) T cells manifested rapid secretion of the Th2 cytokines IL-4, IL-5, and IEL-10, reminiscent of Th2 memory cells. In contrast to wild-type CD4(+) cells, which lost GATA-3 expression when cultured under Th1-polarizing conditions, CD2-GATA3-transgenic CD4(+) cells maintained expression of GATA-3 protein. Under Th1 conditions, cellular proliferation of CD2-GATA3-transgenic CD4(+) cells was severely hampered, IFN-gamma production was decreased and Th2 cytokine production was increased. Enforced GATA-3 expression inhibited Thl-mediated in vivo responses, such as Ag-specific IgG2a production or a delayed-type hypersensitivity response to keyhole limpet hemocyanin. Collectively, these observations indicate that enforced GATA-3 expression selectively inhibits Th1 differentiation and induces Th2 differentiation. The increased functional capacity to secrete Th2 cytokines, along with the increased expression of surface markers for Ag-experienced Th2-committed cells, would argue for a role of GATA-3 in Th2 memory formation.

Original languageEnglish
Pages (from-to)724-732
Number of pages9
JournalJournal of Immunology
Volume167
Issue number2
Publication statusPublished - 15-Jul-2001

Keywords

  • TRANSCRIPTION FACTOR GATA-3
  • BRUTONS TYROSINE KINASE
  • CYTOKINE GENE-EXPRESSION
  • IFN-GAMMA PRODUCTION
  • INTERFERON-GAMMA
  • IMMUNE-RESPONSES
  • NATURAL-KILLER
  • CUTTING EDGE
  • IL-4
  • INTERLEUKIN-4

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