Journal Article•
Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins.
01 Apr 1986-Journal of Immunology (American Association of Immunologists)-Vol. 136, Iss: 7, pp 2348-2357
TL;DR: A panel of antigen-specific mouse helper T cell clones was characterized according to patterns of lymphokine activity production, and two types of T cell were distinguished.
Abstract: A panel of antigen-specific mouse helper T cell clones was characterized according to patterns of lymphokine activity production, and two types of T cell were distinguished. Type 1 T helper cells (TH1) produced IL 2, interferon-gamma, GM-CSF, and IL 3 in response to antigen + presenting cells or to Con A, whereas type 2 helper T cells (TH2) produced IL 3, BSF1, and two other activities unique to the TH2 subset, a mast cell growth factor distinct from IL 3 and a T cell growth factor distinct from IL 2. Clones representing each type of T cell were characterized, and the pattern of lymphokine activities was consistent within each set. The secreted proteins induced by Con A were analyzed by biosynthetic labeling and SDS gel electrophoresis, and significant differences were seen between the two groups of T cell line. Both types of T cell grew in response to alternating cycles of antigen stimulation, followed by growth in IL 2-containing medium. Examples of both types of T cell were also specific for or restricted by the I region of the MHC, and the surface marker phenotype of the majority of both types was Ly-1+, Lyt-2-, L3T4+, Both types of helper T cell could provide help for B cells, but the nature of the help differed. TH1 cells were found among examples of T cell clones specific for chicken RBC and mouse alloantigens. TH2 cells were found among clones specific for mouse alloantigens, fowl gamma-globulin, and KLH. The relationship between these two types of T cells and previously described subsets of T helper cells is discussed.
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TL;DR: Two types of cloned helper T cells are described, defined primarily by differences in the pattern of lymphokines ynthesized, and the different functions of the two types of cells and their lymphokine synthesis are discussed.
Abstract: Effector functions in the immune system are carried out by a variety of cell types, and as our understanding of the complexity of the system expands, the number of recognized subdivisions of cell types also continues to increase. B lymphocytes, producing antibody, were initially distinguished from T lymphocytes, which provide help for B cells (1, 2). The T-cell population was further divided when surface markers allowed separation of helper cells from cytotoxic cells (3). Although there were persistent reports of heterogeneity in the helper T-cell compartment (reviewed below), only relatively recently were distinct types of helper cells resolved. In this review we describe the differences between two types of cloned helper T cells, defined primarily by differences in the pattern of lymphokines ynthesized, and we also discuss the different functions of the two types of cells and their lymphokines. Patterns of lymphokine synthesis are convenient and explicit markers to describe T-cell subclass differences, and evidence increases that many of the functions of helper T cells are predicted by the functions of the lymphokines that they synthesize after activation by antigen and presenting cells. The separation of many mouse helper T-cell clones into these two distinct types is now well established, but their origin in normal T-cell populations is still not clear. Further divisions of helper T cells may have to be recognized before a complete picture of helper T-cell function can be obtained.
7,814 citations
TL;DR: The existence of subsets of CD4+ helper T lymphocytes that differ in their cytokine secretion patterns and effector functions provides a framework for understanding the heterogeneity of normal and pathological immune responses.
Abstract: The existence of subsets of CD4+ helper T lymphocytes that differ in their cytokine secretion patterns and effector functions provides a framework for understanding the heterogeneity of normal and pathological immune responses. Defining the cellular and molecular mechanisms of helper-T-cell differentiation should lead to rational strategies for manipulating immune responses for prophylaxis and therapy.
4,578 citations
TL;DR: Recently, substantial advances in the understanding of the molecular pathogenesis of inflammatory bowel disease (IBD) have been made owing to three related lines of investigation as mentioned in this paper, which have shown the importance of epithelial barrier function, and innate and adaptive immunity in disease pathogenesis.
Abstract: Recently, substantial advances in the understanding of the molecular pathogenesis of inflammatory bowel disease (IBD) have been made owing to three related lines of investigation. First, IBD has been found to be the most tractable of complex disorders for discovering susceptibility genes, and these have shown the importance of epithelial barrier function, and innate and adaptive immunity in disease pathogenesis. Second, efforts directed towards the identification of environmental factors implicate commensal bacteria (or their products), rather than conventional pathogens, as drivers of dysregulated immunity and IBD. Third, murine models, which exhibit many of the features of ulcerative colitis and seem to be bacteria-driven, have helped unravel the pathogenesis/mucosal immunopathology of IBD.
3,831 citations
TL;DR: The increasing number of T-cell subsets defined by cytokine patterns; the differentiation pathways of CD4+ and CD8+ T cells; the contribution of other cell types to these patterns; and the cytokine interactions during infection and pregnancy are discussed.
3,815 citations
TL;DR: It is shown that chronic activation of both human and murine CD4+T cells in the presence of interleukin (IL)-10 gives rise to CD4-T-cell clones with low proliferative capacity, producing high levels ofIL-10, low levels of IL-2 and no IL-4.
Abstract: Induction and maintenance of peripheral tolerance are important mechanisms to maintain the balance of the immune system. In addition to the deletion of T cells and their failure to respond in certain circumstances, active suppression mediated by T cells or T-cell factors has been proposed as a mechanism for maintaining peripheral tolerance. However, the inability to isolate and clone regulatory T cells involved in antigen-specific inhibition of immune responses has made it difficult to understand the mechanisms underlying such active suppression. Here we show that chronic activation of both human and murine CD4+ T cells in the presence of interleukin (IL)-10 gives rise to CD4+ T-cell clones with low proliferative capacity, producing high levels of IL-10, low levels of IL-2 and no IL-4. These antigen-specific T-cell clones suppress the proliferation of CD4+ T cells in response to antigen, and prevent colitis induced in SCID mice by pathogenic CD4+CD45RB(high) splenic T cells. Thus IL-10 drives the generation of a CD4+ T-cell subset, designated T regulatory cells 1 (Tr1), which suppresses antigen-specific immune responses and actively downregulates a pathological immune response in vivo.
3,782 citations
References
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TL;DR: It is demonstrated that B cell stimulatory factor (BSF-1) and B cell differentiation factor (BCDF-gamma) are the same lymphokine and that BSF-1 acts on both resting and activated B cells to induce different effects.
Abstract: By three criteria, we have demonstrated that B cell stimulatory factor (BSF-1) and B cell differentiation factor (BCDF-gamma) are the same lymphokine. Highly purified preparations of high performance liquid chromatography-purified or affinity-purified BSF-1 had BCDF-gamma activity but not BCDF-mu activity. A monoclonal anti-BSF-1 antibody coupled to Sepharose depleted both BSF-1 and BCDF-gamma activity but not BCDF-mu activity from two different T cell supernatants. Soluble monoclonal anti-BSF-1 blocked the BSF-1 and BCDF-gamma but not the BCDF-mu responses. These results suggest that BSF-1 acts on both resting and activated B cells to induce different effects.
388 citations
TL;DR: Differences in activation requirements observed for the Lyb-5- and LyB- 5+ B cell subsets do not result from differences in the TH cell populations activating these B cells, but rather reflect differences inThe ability ofThese B cells to respond to signals from the same TH cells.
Abstract: It has recently been demonstrated that the Lyb-5+ and Lyb-5- B cell subpopulations differ in their requirements for major histocompatibility complex (MHC)-restricted activation by T helper (TH) cells. To determine whether these MHC-restricted and -unrestricted pathways of B cell activation result from differences in the participating TH cell populations or reflect differences exclusively in the responding B cell subpopulations, experiments were carried out using cloned TH cells for in vitro antibody responses to trinitrophenyl-keyhole limpet hemocyanin. The same cloned T helper cells were able to activate both CBA/N (Lyb-5-) B cells and CBA/CaHN (Lyb-5+ + Lyb-5-) B cells under different experimental conditions. The activation of Lyb-5-B cells by cloned T helper cells required both MHC-restricted TH cell-B cell interaction and carrier-hapten linkage. In contrast, the activation of Lyb-5+ B cells required only MHC-restricted T helper cell interaction with accessory cells, while T-B interaction was MHC unrestricted and did not require carrier-hapten linkage. Thus, the differences in activation requirements observed for the Lyb-5- and Lyb-5+ B cell subsets do not result from differences in the TH cell populations activating these B cells, but rather reflect differences in the ability of these B cells to respond to signals from the same TH cells.
46 citations
TL;DR: The specificity pattern suggested that the T-cell clones recognized a more restricted set of cRBC MHC-associated allodeterminants than do antibody-producing cells, which required antigen processing and were MHC restricted and antigen dose dependent.
31 citations
Journal Article•
TL;DR: The I-At molecule is shielded by trypsin-labile material on some T cells, whereas on others it is fully exposed, and the transition from a shielded to an exposed configuration may correlate with T cell activation.
Abstract: An I-A subregion-controlled structure (I-At) characterizes some helper T cells and augmenting factors This epitope is associated with a glycoprotein Extended trypsin digestion removed the determinant; tunicamycin blocked its reexpression In contrast, limited trypsinization increased the number of I-At-bearing peripheral T cells from 17 to 35% The I-At molecule density on cells expressing this structure did not change measurably with limited enzyme treatment Rather, some previously negative T cells (20%) expressed the epitope after mild proteolysis A third T cell subset (60%) expressed no I-At molecules regardless of enzyme treatment We conclude that the I-At molecule is shielded by trypsin-labile material on some T cells, whereas on others it is fully exposed The transition from a shielded to an exposed configuration may correlate with T cell activation Cycloheximide inhibited the biosynthesis of both the I-At molecule and the shielding substance by T cells Unlike I-A-controlled T cell structures, B cell I-A-encoded molecules are neither shielded nor trypsin labile The relationship between I region-controlled T cell and B cell molecules is discussed
5 citations