INDUCTION OF TH1 AND TH2 CD4⁺T CELL RESPONSES:The Alternative Approaches

Abstract

▪ Abstract T helper lymphocytes can be divided into two distinct subsets of effector cells based on their functional capabilities and the profile of cytokines they produce. The Th1 subset of CD4+ T cells secretes cytokines usually associated with inflammation, such as IFN-γ and TNF and induces cell-mediated immune responses. The Th2 subset produces cytokines such as IL-4 and IL-5 that help B cells to proliferate and differentiate and is associated with humoral-type immune responses. The selective differentiation of either subset is established during priming and can be significantly influenced by a variety of factors. One of these factors, the cytokine environment, has been put forward as the major variable influencing Th development and is already well reviewed by others. Instead, in the current review, we focus on some of the alternative approaches for skewing Th1/Th2 responses. Specifically, we discuss the effects on Th priming of (a) using altered peptide ligands as antigens, (b) varying the dose of antigen, and (c) altering costimulatory signals. The potential importance of each of these variables to influence immune responses to pathogens in vivo is discussed throughout.

Similar inflammatory DC maturation signatures induced by TNF or Trypanosoma brucei antigens instruct default Th2‐cell responses

“…However, since these quantitative changes led to qualitatively different Th1 or Th2-cell polarization, this may reflect another DC-based aspect of the ''strength of signal'' theory where peptide titrations and affinities heavily influenced the Th-cell skewing potential [59,60]. The peptide dose dependency has been shown to be independent of the DC subtype but strong LPS or CpG stimulation clearly shifted toward Th1-cell [61].…”

Prolonged exposure of dendritic cells to maturation stimuli favors the induction of type‐2 cytotoxic T lymphocytes

“…1C, D), whereas CD8 + T cells producing both IFN-c and a Tc2 cytokine were <5% (data not shown). The role of TCR/MHC interactions in T cell polarization is well recognized [36]. Hence, we assessed the capacity of DC at various activation stages to induce polarization of a transgenic T cell population with a different specificity, i.e.…”

“…Hence, we assessed the capacity of DC at various activation stages to induce polarization of a transgenic T cell population with a different specificity, i.e. cells from TCR7 mice expressing a TCR specific for the epitope 33-41 of lymphocytic choriomeningitis virus (LCMV) glycoprotein 1 (gp [33][34][35][36][37][38][39][40][41] ) [37,38]. In this set of experiments we also tested CpG as pro-maturation stimulus (see Supplementary Fig.…”

“…DO11.10 mice express a Tg ab TCR specific for OVA 323-339 presented in the context of I-A d molecules. LCMV gp33 mice, which express a TCR specific for gp [33][34][35][36][37][38][39][40][41] in association with H-2D b [37], were backcrossed onto C57BL/6 background over six generations to obtain TCR7 mice [38]. All mice were housed in a specific pathogen-free animal facility, and treated in accordance with the European Union Guidelines together with the approval of the Institutional Ethics Committee.…”

Linkage analysis of the genetic determinants of T-cell IL-4 secretion, and identification of Flj20274 as a putative candidate gene

“…5 The action of these critical cytokines is characterized by reciprocal inhibition of opposing Th subsets and progressive stabilization of developing Th populations. 2 In addition, Th cell fates may also be influenced by features of the T cell-APC interaction such as the APC cell type, 6 relative strength of TCR signalling, 7 ligation of specific costimulatory receptors 8 and organization of membrane microdomains. 9 Ultimately, all of these regulatory influences are integrated in the nucleus by the recruitment of Th subsetspecific transcription factors at conformationally receptive chromatin (reviewed in O'Garra and Arai 10 ), in order to initiate the expression of defining cytokine genes.…”