Our previous in vivo studies show that both the amount of Ag and the number of available naive CD4 T cells affect the Th1/Th2 phenotype of the effector CD4 T cells generated. We examined how the number of OVA-specific CD4 TCR transgenic T cells affects the Th1/Th2 phenotype of anti-SRBC CD4 T cells generated in vivo upon immunization with different amounts of OVA-SRBC. Our observations show tha...

The commitment of naive T cells to polarized Th cells requires specific changes in their transcription factors. Retrovirally overexpressed GATA-3 has been reported to induce the Th2 cytokine profile in developing Th1 cells. In this study, we examined the role of the N-terminal finger (Nf) of GATA-3 in Th2 cell development. The Nf, as well as the C-terminal finger and the transactivation domain,...

Immune responses may be qualitatively distinct depending on whether Th1 or Th2 cells predominate at the site of Ag exposure. T cell subset-specific expression of ligands for vascular selectins may underlie the distinct patterns of recruitment of Th1 or Th2 cells to peripheral inflammatory sites. Here we examine the regulation of selectin ligand expression during murine T helper cell differentia...

The development of CD4+ T helper (Th) type 1 and 2 cells is essential for the eradication of pathogens, but can also be responsible for various pathological disorders. Therefore, modulation of Th cell differentiation may have clinical utility in the treatment of human disease. Here, we show that interleukin (IL) 12 and IL-4 directly induce human neonatal CD4- T cells, activated via CD3 and CD28...

An initial activation signal via the TCR in a restricted cytokine environment is critical for the onset of Th cell development. Cytokines regulate the expression of key transcriptional factors, T-bet and GATA-3, which instruct the direction of Th1 and Th2 differentiation, through changes in chromatin conformation. In this study, we investigated the kinetics of IL-4-mediated signaling in a trans...

Rheumatoid arthritis (RA) is the most common autoimmune disorder. Loss of Th1/Th2 and Th17/Treg balance has been reported in several inflammatory autoimmune diseases. This study was to investigate Th1, Th2, Th17, and Treg differentiation and related cytokines in RA patients. The frequencies of Th1, Th2, Th17, and Treg cells in peripheral blood of RA patients (n = 76) and healthy controls (n = 1...

The development of Schistosoma mansoni ova-induced granulomas is regulated by cytokines secreted by distinct Th cell subsets. To determine the importance of Th1 and Th2 cells in granuloma formation, we have studied the immune response to S. mansoni ova in Stat4- and Stat6-deficient mice, which lack Th1 and Th2 cells, respectively. Lymphocytes from both naive and infected Stat6-deficient mice pr...

The delineation of the in vivo role of GATA-3 in human T cell differentiation is a critical step in the understanding of molecular mechanisms directing human immune responses. We examined T cell differentiation and T cell-mediated effector functions in individuals lacking one functional GATA-3 allele. CD4 T cells from GATA-3+/- individuals expressed significantly reduced levels of GATA-3, assoc...

Abstract Helminth parasites induce potent host type 2 immune responses (T2I) that promote parasite clearance and prevent reinfection. The parasite-induced T2I involve both innate adaptive cell components, but how the activation of different types is coordinated during initiation incompletely understood. Dendritic cells (DCs) are best known for their role in bridging immunity by sensing immunolo...