Functional heterogeneity of CD4-positive T-cell subsets: The correlation between effector functions and lymphokine secretion is limited

Erb, Peter C.; Troxler, Monica; Fluri, Monika; Grogg, Daniel; Alkan, Şefik Ş.

doi:10.1016/0008-8749(91)90268-g

Cited by 14 publications

(5 citation statements)

References 42 publications

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“…The CD4 + CD45RC + T cell subset produces IL-2 and IFN-γ and in this respect resembles the T helper 1 subset of mouse CD4 + T cells, which can mediate delayedtype hypersensitivity and CD4 + T-cell cytotoxicity (Erb et al 1990). This subset also includes naive or unprimed T lymphocytes (Powrie and Mason 1988).…”

Section: Discussionmentioning

confidence: 99%

Expression of CD45RC and Ia antigen in the spinal cord in acute experimental allergic encephalomyelitis: An immunocytochemical and flow cytometric study

McCombe

Fordyce

Jersey

et al. 1992

Journal of the Neurological Sciences

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We performed immunocytochemical studies to analyze the inflammatory infiltrate and major histocompatibility complex class II (Ia) antigen expression in the spinal cord of Lewis rats with acute experimental allergic encephalomyelitis (EAE) induced by inoculation with myelin basic protein and adjuvants. Using antibodies to lymphocyte markers and other monoclonal antibodies we found that during clinical episodes the inflammatory infiltrate was chiefly composed of T lymphocytes and macrophages. The majority of cells in the inflammatory infiltrate were stained by the W3/25 antibody to CD4 and a proportion was stained by OX22 which labels the high molecular weight form of the leucocyte common antigen (CD45RC). CDB+ T cells were sparse and B cells were not detected. There was minimal staining with the OX39 antibody to the interleukin-2 receptor. Presumptive microglia, identified by their dendritic morphology, expressed Ia antigen during the clinical episodes and after recovery. The prominence of Ia antigen expression after recovery could indicate that this la expression was associated with downregulation of the encephalitogenic immune response. We also performed flow cytometry studies on cells extracted from the spinal cord of rats before and during attacks of EAE. With flow cytometry, we found that in established disease a mean of 83(SD, 23)% of CD2+ cells were CD4+, and a mean of 27(SD, 12)% of CD2+ cells were CD45RC+. In rats sampled on the first day of signs, a mean of 43(SD, 22)% of CD2+ cells were CD45RC+. In the cells extracted from the spinal cord of rats with established disease a mean of 47(SD, 32)% of macrophages were CD45RC+. Our study has combined an immunocytochemical assessment of tissue sections with quantitative flow cytometry assessment of cells extracted from the spinal cord of rats with acute EAE. We have shown that the majority of T lymphocytes in the spinal cord are CD45RC − . We have also found prominent Ia expression on dendritic cells in acute EAE and after clinical recovery.

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Section: Discussionmentioning

confidence: 99%

Expression of CD45RC and Ia antigen in the spinal cord in acute experimental allergic encephalomyelitis: An immunocytochemical and flow cytometric study

McCombe

Fordyce

Jersey

et al. 1992

Journal of the Neurological Sciences

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“…The ovalbumin (OVA)-specific I-Ad-restricted T cell hybrid 4E12 was generated by fusing an OVA-specific Tcell line derived from a BIO.D2/0 mouse with the HAT-sensitive BW 5147 lymphoma. Hybrid 10H/A.H restricted by I-Ad and specific for keyhole limpet hemocyanin (KLH) was derived by fusing T cell clone 10H/A [7] (kindly provided by Dr. P. Erb, Basel) with BW 5147. Hybrid lES.ll specific for hen egg lysozyme (HEL) in the context of I-Ed [8] was a gift from Dr. L. Adorini (Sandoz, Basel).…”

Section: Introductionmentioning

confidence: 99%

Capacity of antigen uptake by B cells, fibroblasts or macrophages determines efficiency of presentation of a soluble self antigen (C5) to T lymphocytes

Stockinger¹

1992

Eur J Immunol

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Self antigens in the body fluids must be taken up, processed and presented by antigen-presenting cells (APC) in order to induce T cell tolerance. For self antigens like the fifth component of complement (C5) which is not picked up by APC via antigen-specific receptors, presentation has to rely on uptake by nonspecific means. C5 was used as a model soluble self antigen to study the capacity of different APC (B lymphoma cells, fibroblasts and macrophages) of taking up, processing and presenting low concentrations of soluble C5 to C5 specific T cell hybrids. Under conditions of limiting antigen amounts macrophages and fibroblasts exhibited similar presentation capacity for soluble C5 while B cells did not. C5 presentation by macrophages was enhanced in the presence of C5-specific antibody and augmented further if antigen was added in the form of particulate latex-antigen-antibody complexes indicating enhanced uptake via Fc receptor-mediated endocytosis or phagocytosis. B cells presented soluble C5 only in the presence of C5-specific antibody. Uptake of C5 under these conditions occurred via Fc receptors type II. This pathway of antigen uptake did not operate with other antigens which were presented efficiently after nonspecific endocytosis. In light of these findings it seems reasonable to propose that nonspecific endocytosis of serum proteins like C5 by B cells is normally limited in order to avoid interference with their critical role in antigen receptor-mediated uptake and presentation for the initiation of an antibody response. It seems likely that presentation of soluble self antigens present in the circulation may normally be the task of dendritic cells and macrophages depending on the physical shape of the antigen.

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“…Transfection experiments have shown that expression of exogenous Trk rescues NGF responsiveness in mutant NGF-nonresponsive rat pheochromocytoma PC12 cells (26). This finding is in line with the ability of Trk to initiate both differentiation and mitogenesis in heterologous cell systems such as Xenopus oocytes (27) and mouse 3T3 fibroblasts (28) rine keyhole limpet hemocyanin (KLH)-specific T-cell clones 8/37 [T helper (Th) 0 type] 9/6 and 9/9 (both Thl type) and of conalbumin-specific T-cell clone D1O.G4.1 (Th2 type; ATCC TIB 224) have been described elsewhere (32,33). Approximately 5 x 106 T cells were activated either with Con A (5 ,ug/ml) or with the specific antigen (50 ,ug/ml) plus 5 x 106 irradiated (3000 rad; 1 rad = 0.01 Gy) antigen-presenting cells (APCs) in Iscove's medium (GIBCO) containing 10% (vol/vol) fetal calf serum and 50 ,uM 2-mercaptoethanol.…”

mentioning

confidence: 99%

“…The major histocompatibility complex class II-positive B lymphoma A20.2J was used as the APC for T-cell clones 8/37, 9/6, and 9/9, and TA3 cells were used for clone D1O.G4.1. The doses of mitogen and of antigen and the number of APCs used were optimal to activate T cells for IL production (32).…”

mentioning

confidence: 99%

Expression of nerve growth factor and nerve growth factor receptor tyrosine kinase Trk in activated CD4-positive T-cell clones.

Ehrhard

Erb

Graumann

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

291

172

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Recent evidence suggests that nerve growth factor (NGF), in addition to its neurotrophic functions, acts as an immunomodulator mediating "cross-talk" between neuronal and immune cells, including T lymphocytes. We have analyzed murine CD4+ T-cell clones for their ability to express transcripts encoding NGF, low-affinity NGF receptor, and trk protooncogene, the signal-transducing receptor subunit for NGF. We show that two CD4+ T-helper (Th) Nerve growth factor (NGF), the best characterized member of a family of neurotrophic factors, is required for the differentiation and survival of sympathetic and some sensory and cholinergic neuronal populations (1). In addition to its neurotrophic effects, there is accumulating evidence that NGF is involved in inflammatory responses. For example, NGF increases the number of mast cells in neonatal rats (2), leads to a massive degranulation of rat peritoneal mast cells (3-5), promotes differentiation of specific granulocytes (6), and stimulates wound healing (7). Treatment of young rats with NGF before and after immunization with sheep erythrocytes results in an enhancement of T-lymphocytedependent antibody synthesis (8). In addition, NGF has been shown to enhance lymphocyte proliferation in both B-and T-cell populations (9-11) and to stimulate production of IgG4 (12). These data implicate NGF in the modulation of humoral and cell-mediated immune responses.Studies on the regulatory mechanisms involved in NGF production reveal that inflammatory stimuli contribute significantly to an increased NGF production (13). Interleukin 1 (IL-1), a mediator of inflammation and tissue degradation, is a potent inducer of NGF synthesis in the rat sciatic nerve (14) and in the central nervous system (15). IL-1 (16) and IL-6 (17) both induce increased production and secretion ofbiologically active NGF by astrocytes. The findings that activated rat peritoneal macrophages (18)

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Functional heterogeneity of CD4-positive T-cell subsets: The correlation between effector functions and lymphokine secretion is limited

Cited by 14 publications

References 42 publications

Expression of CD45RC and Ia antigen in the spinal cord in acute experimental allergic encephalomyelitis: An immunocytochemical and flow cytometric study

Expression of CD45RC and Ia antigen in the spinal cord in acute experimental allergic encephalomyelitis: An immunocytochemical and flow cytometric study

Capacity of antigen uptake by B cells, fibroblasts or macrophages determines efficiency of presentation of a soluble self antigen (C5) to T lymphocytes

Expression of nerve growth factor and nerve growth factor receptor tyrosine kinase Trk in activated CD4-positive T-cell clones.

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