Molecular Mechanisms RegulatinG Th1 Immune Responses

Abstract

The T helper lymphocyte is responsible for orchestrating the appropriate immune response to a wide variety of pathogens. The recognition of the polarized T helper cell subsets Th1 and Th2 has led to an understanding of the role of these cells in coordinating a variety of immune responses, both in responses to pathogens and in autoimmune and allergic disease. Here, we discuss the mechanisms that control lineage commitment to the Th1 phenotype. What has recently emerged is a rich understanding of the cytokines, receptors, signal transduction pathways, and transcription factors involved in Th1 differentiation. Although the picture is still incomplete, the basic pathways leading to Th1 differentiation can now be understood in in vitro and a number of infection and disease models.

Interleukin‐4 regulates proteoglycan‐induced arthritis by specifically suppressing the innate immune response

“…We specifically tested the requirement for IFN␥ because development of PGIA is dependent on IFN␥ and STAT-4, and IL-4 has been shown to inhibit several components of the Th1 pathway, in particular STAT-4, IL-12R␤2, and T-box expressed in T cells (T-bet) (7,18). T cell IL-2 production was assessed in culture supernatants from T cells activated with human PG in the presence of irradiated naive splenocytes.…”

“…IL-4 has been shown to inhibit STAT-4 induction, IL-12R␤2 expression, and the transcription factor T-bet (18). Moreover, the quantity of IFN␥ produced was associated with the magnitude of the PG-specific IgG2a isotype (8).…”

Dynamic Balance of pSTAT1 and pSTAT3 in C57BL/6 Mice Infected with Lethal Or Nonlethal Plasmodium yoelii

“…STAT1, the first known member of STAT family, is a principal target of both type I and type II interferons (IFNs). It is critically involved in the initiation of Th1 inflammatory cascade (18)(19)(20)(21)(22). Activation of STAT1 promotes the activation of dentritic cells (DCs) (22,23) and natural killer (NK) cells (24), and inhibits the development of regulatory T cells (25,26).…”

A stage‐specific functional role of the leucine zipper transcription factor c‐Maf in lung Th2 cell differentiation

“…In contrast to Th1 cells, which produce large amounts of IFN-c, Th2 cells are known to produce the signature cytokines IL-4, IL-5 and IL-13 [5,[9][10]. Increased numbers of CD4 + T cells expressing IL-4 and IL-5 have been found in the airways of asthmatic subjects [2].…”