Helper T lymphocyte

About: Helper T lymphocyte is a research topic. Over the lifetime, 1334 publications have been published within this topic receiving 63295 citations.

Functional diversity of helper T lymphocytes.

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.

Massive covert infection of helper T lymphocytes and macrophages by HIV during the incubation period of AIDS

Abstract: ANIMAL and human lentiviruses elude host defences by establishing covert infections and eventually cause disease through cumulative losses of cells that die with activation of viral gene expression1–5. We used polymerase chain reaction in situ double-label methods6,7 to determine how many CD4+ lymphocytes are latently infected by human immunodeficiency virus (HIV) in patient lymph nodes and whether the pool of infected cells is large enough to account for immune depletion through continual activation of viral gene expression and attrition of cells responding to antigens. We discovered an extraordinarily large number of latently infected CD4+ lymphocytes and macrophages throughout the lymphoid system from early to late stages of infection, and confirmed8–14 the extracellular association of HIV with follicular dendritic cells. Follicular dendritic cells may transmit infection to cells as they migrate through lymphoid follicles. Latently infected lymphocytes and macrophages constitute an intracellular reservoir large enough ultimately to contribute to much of the immune depletion in AIDS, and represent a difficult problem that must be resolved in developing effective treatments and protective vaccine.

Anti-proliferative effect of IFN-gamma in immune regulation. I. IFN-gamma inhibits the proliferation of Th2 but not Th1 murine helper T lymphocyte clones.

Abstract: A biphasic dose-response curve was observed when the IL-1-dependent HTL clone D10 was exposed to IL-1 plus supernatants from some activated T cell clones but not others. The active component that inhibited proliferation at high concentrations of these supernatants appeared to be IFN-gamma based on the following findings: 1) the biphasic pattern of responsiveness correlated with the presence of IFN-gamma in the supernatants; 2) an anti-IFN-gamma mAb augmented the proliferation of D10 cells to these supernatants; 3) rIFN-gamma inhibited profoundly the response of D10 cells stimulated with rIL-1 plus supernatant from activated D10 cells or with rIL-1 plus rIL-4; 4) the response of D10 cells to rIL-1 plus rIL-2 also was inhibited by rIFN-gamma, although to a lesser extent. The proliferation of an additional Th2 clone stimulated with rIL-1 plus rIL-4 or rIL-2 also was inhibited by rIFN-gamma, implicating IFN-gamma as an inhibitory lymphokine for Th2 cells in general. rIFN-gamma did not affect the proliferation of two Th1 clones, nor did it affect the proliferation of an unconventional HTL clone which produces both IL-4 and IFN-gamma and proliferates in response to IL-2 or IL-4 in an IL-1-independent fashion. The proliferation of D10 cells stimulated by Ag or by immobilized anti-CD3 antibody also was blocked by rIFN-gamma, whereas IL-4 production in response to these stimuli was unaffected, indicating that proliferation and not general cell function was specifically inhibited. Collectively, these data implicate IFN-gamma as a suppressive factor for the proliferation of the subset of HTL designated Th2, and suggest that the relative amounts of the various lymphokines present during an immune response may direct which T cell types increase in number.

Pulmonary sarcoidosis: a disorder mediated by excess helper T-lymphocyte activity at sites of disease activity.

Abstract: Using the monoclonal antibodies OKT4 and OKT8, we determined the proportions of helper and suppressor T cells in patients with sarcoidosis and high-intensity alveolitis, patients with sarcoidosis and low-intensity alveolitis, patients with idiopathic pulmonary fibrosis (IPF), and normal controls. In controls and patients with IPF, the ratio of helper to suppressor T cells was 1.8:1 in lungs and blood. In contrast, this ratio was 10.5:1 in lungs (P less than 0.001) and 0.8:1 in blood (P less than 0.05) in patients with sarcoidosis and high-intensity alveolitis. The ratio of helper to suppressor T cells was not higher in the lungs or blood of patients with sarcoidosis and low-intensity alveolitis; on the contrary, because of the higher proportions of suppressor cells, the ratio of helper to suppressor cells was lower in both lungs and blood. In studies of function, lung T cells from patients with sarcoidosis and high-intensity alveolitis released monocyte chemotactic factor (a lymphokine critical to granuloma formation) and polyclonally activated B cells to produce immunoglobulins. We conclude that one determinant of lung injury in sarcoidosis in the presence of large numbers of lung helper T cells, which are important in granuloma formation.

Lineage commitment in the immune system: the T helper lymphocyte grows up

Abstract: Cells of the immune system provide particularly fruitful subjects for the study of lineage commitment. Both T and B lymphocytes undergo complicated patterns of differentiation from uncommitted, nonfunctional precursor cells to highly sophisticated effector cells. The development of the helper T lymphocyte is one of the most elegant examples of this. A little over a decade ago, Mosmann and Coffman (1989) discovered that naive mouse CD4 T helper lymphocytes, upon receiving an antigenic stimulus, differentiate into two distinct subsets defined both by their function and by unique cytokine profiles. These subsets, T helper 1 (Th1) and T helper 2 (Th2) (Mosmann et al. 1986; Mosmann and Coffman 1989; Paul and Seder 1994; O’Garra 1998; Rengarajan and Glimcher 2000), are responsible for cell-mediated/inflammatory immunity and humoral responses, respectively (Fig. 1). This division of labor fits nicely with previous demonstrations that an organism tends to mount either a cell-mediated or humoral response, but not both, in response to pathogens. The function of T helper cells can largely be explained by the cytokines they secrete. Cytokines (or lymphokines) are small hormone-like polypeptides that have pleiotrophic biological activities in several cell types. Resting T cells do not transcribe cytokine genes, but they are rapidly induced upon coactivation through the T-cell receptor (TCR) and costimulatory receptors (Lenschow et al. 1996). Much progress has been made in identifying the signaling pathways and transcription factors that control Th1 and Th2 differentiation as shown schematically (Fig. 2a). This review will summarize what is currently known about the signals that regulate lineage commitment in T helper cells with a special focus on three subset-specific transcription factors, T-bet, GATA-3, and c-Maf, responsible for lineage commitment (Fig. 2b).