Parameters of cellular immunity in perimenopausal patients with glandular and adenomatous endometrial hyperplasia

No appreciable disorders of cellular immunity were detected in patients with glandular cystic endometrial hyperplasia. Atypical endometrial hyperplasia was associated with quantitative changes in T lymphocytes and their subpopulations, decreased level of lymphocytes carrying activation antigens, and increased count of natural killers. These changes can be characterized as immunocompensation.     

Local immune responses and systemic cytokine responses in zoster: relationship to the development of postherpetic neuralgia

Varicella zoster virus (VZV) causes varicella (chickenpox) as the primary infection and zoster (shingles) on reactivation from latency, often many years later. One of the most common and most severe sequela of zoster is postherpetic neuralgia (PHN). Apart from age, factors which predispose towards PHN are unknown. In the present study, the concentration of a variety of Th1 and Th2 cytokines in the serum of 30 zoster patients at the time of the acute disease were correlated with the subsequent development of PHN in nine of these patients, but no association was found. In addition, although some cytokines such as IFN-gamma, IL-6 and IL-8 were slightly raised in the zoster group compared with a group of normal healthy subjects of a similar age distribution, these differences only verged on significance. Antibody titres to VZV were raised in the zoster group compared with the controls but these did not differ between the patients who developed PHN and those who did not. Biopsies of zoster lesions were collected from nine patients. There were significantly fewer infiltrating lymphocytes in the lesions of the three patients who subsequently developed PHN compared with the six who did not, although the expression of the neuropeptide, substance P, did not differ between the two groups. It is possible that the poor inflammatory response at the time of the acute zoster may result in less effective containment of the VZV and more damage in the dermatome, thus contributing to the persistence of the neuralgia.     

T cell stimulation in the absence of exogenous antigen: a T cell signal is induced by both MHC-dependent and -independent mechanisms

Mature T cells residing in peripheral lymphoid organs have frequent contact with antigen presenting cells (APC). Such contact may be required for T cell survival, but the degree to which signals in mature T cells are induced by TCR recognition of self peptide/MHC complexes is unclear. We have used induction of the early growth response gene 1 (Egr1) as an indicator of signal transduction in 3.L2 (I-Ek-restricted) T cells interacting with APC in the absence of exogenous antigen. The data show that Egr1 can be induced in 3.L2 T cells by TCR recognition of self peptides presented by I-Ek. However, a more transient induction of Egr1 can be induced in 3.L2 T cells interacting with dendritic cells derived from class II/beta2m double-deficient mice. Egr1 induction after T cell-APC contact was also observed in a freshly isolated polyclonal CD4 T cell population. The data suggest that self peptide/MHC recognition by the TCR induces a signal in T cells and that dendritic cells can also induce a more transient T cell signal by an MHC-independent mechanism.     

ACh receptor protein drives primary and memory autoantibody responses in chimeric human-SCID mice

The native antigen that drives the T-helper cells regulating production of muscle acetylcholine receptor (AChR) autoantibodies is unknown. Human T cell lines activated by autoantigens in vitro are of unproven relevance to B cell help. Here we report the functional interaction and unprecedented longevity of AChR-specific human T and B lymphocytes residing in SCID mice. Lymphoid cells from myasthenia gravis (MG) patients and healthy subjects were injected ip. Recombinant human AChR-alpha1-subunit-1-210 was injected after day 75. Human AChR-specific Ig was produced rapidly in MG-SCID mice challenged once. Only 1 of 32 control hu-SCID mice produced AChR-specific Ig. This required multiple immunizations, was initially cross-reactive with Torpedo AChR, and had a slow course. Thus, memory T and B lymphocytes specific for human AChR-alpha1-subunit are readily demonstrable in MG patients, interact to produce autoantibody of the same restricted specificity found in the donor's serum, and are long-lived without exogenous autoantigen challenge. In healthy subjects, AChR-specific lymphocytes are infrequent and exhibit naive response characteristics, including apparent affinity maturation of Ig specificity.     

CYFIP2 is highly abundant in CD4+ cells from multiple sclerosis patients and is involved in T cell adhesion

DNA microarray profiling of CD4(+) and CD8(+) cells from non-treated relapsing and remitting multiple sclerosis (MS) patients determined that the cytoplasmic binding partner of fragile X protein (CYFIP2, also called PIR121) was increased significantly compared to healthy controls. Western analysis confirmed that CYFIP2 protein was increased approximately fourfold in CD4(+) cells from MS compared to inflammatory bowel disorder (IBD) patients or healthy controls. Because CYFIP2 acts as part of a tetrameric complex that regulates WAVE1 activation we hypothesized that high levels of CYFIP2 facilitate T cell adhesion, which is elevated in MS patients. Several findings indicated that increased levels of CYFIP2 facilitated adhesion. First, adenoviral-mediated overexpression of CYFIP2 in Jurkat cells increased fibronectin-mediated adhesion. Secondly, CYFIP2 knock-down experiments using antisense oligodeoxynucleotides reduced fibronectin-mediated binding in Jurkat and CD4(+) cells. Thirdly, inhibition of Rac-1, a physical partner with CYFIP2 and regulator of WAVE1 activity, reduced fibronectin-mediated adhesion in Jurkat and CD4(+) cells. Finally, inhibition of Rac-1 or reduction of CYFIP2 protein decreased fibronectin-mediated adhesion in CD4(+) cells from MS patients to levels similar to controls. These studies suggest that overabundance of CYFIP2 protein facilitates increased adhesion properties of T cells from MS patients.     

Distinct expression patterns of polycomb oncoproteins and their binding partners during the germinal center reaction

Polycomb group (PcG) genes encode two chromatin-binding protein complexes, the PRC1 and the PRC2 PcG complexes, which are essential for the maintenance of cell identity and play a role in oncogenesis. PcG complexes were recently identified as novel regulators of hematopoiesis, and appear to be expressed in a non-overlapping pattern in resting and mature follicular B cells. Using highly specific antisera in combination with immunohistochemistry and triple immunofluorescence, we investigated the expression pattern of nine human PcG genes in germinal center (GC) B cells and highly purified germinal center B cell subpopulations. PcG proteins were detected in characteristic binding patterns that were not necessarily related to mutually exclusive expression of the two PcG complexes. We conclude that the two PcG complexes are expressed throughout GC development, and that the fine composition of each complex is determined by the differentiation status of the cell. In addition, a subset of dividing cells with a centrocyte CD marker profile was identified that co-expresses core components of the PRC1 and PRC2 complex. We propose that these cells reflect a transitional stage between resting and dividing follicular B lymphocytes, and that they possibly represent the healthy precursors of nodal large B cell lymphomas.     

A Novel Lymphocyte Signaling Defect: trk A Mutation in the Syndrome of Congenital Insensitivity to Pain and Anhidrosis (CIPA)

Congenital insensitivity to pain with anhidrosis is a syndrome characterized by loss of pain and sensation. The condition frequently evolves into deep wounds and prolonged healing times. Anhidrosis is another prominent component of the disorder. Often associated with recurrent episodes of unexplained fever, it can result in patient mortality. Recent investigations point to Trk A, the high affinity receptor for nerve growth factor (NGF), as a candidate for the site of the mutation that causes the disorder. Functional NGF receptors, such as Trk A and the Trk family of tyrosine kinases, are essential for NGF signaling of human lymphocytes. In this study, we demonstrated that the presence of a trk A mutation in patient B cells results in a novel lymphocyte signaling defect. In these B cells, NGF failed to induce Trk A phosphorylation, cytoskeleton assembly, or MAP kinase activation. These abnormalities may explain some of the clinical features of the disease.     

Allergen immunotherapy induces a suppressive memory response mediated by IL-10 in a mouse asthma model

BACKGROUND: Human studies have demonstrated that allergen immunotherapy induces memory suppressive responses and IL-10 production by allergen-specific T cells. Previously, we established a mouse model in which allergen immunotherapy was effective in the suppression of allergen-induced asthma manifestations. OBJECTIVE: In this study, we examined whether immunotherapy induces a long-lasting effect and investigated the role of IL-10 in successful immunotherapy. METHODS: Ovalbumin-sensitized BALB/c mice were treated with 3 injections of ovalbumin (1 mg, subcutaneous) on alternate days. After a short interval (1 week) and after a long interval (5 weeks), mice were challenged by ovalbumin inhalation, and subsequently, airway reactivity, airway eosinophilia, ovalbumin-specific IgE, and T(H)2 cytokine profile were measured. Flow cytometry and blocking of IL-10 receptors in vivo were used to gain insight in the role of IL-10 in the beneficial effects of allergen immunotherapy. RESULTS: After a long interval between ovalbumin immunotherapy and ovalbumin challenge, the development of airway eosinophilia and hyperresponsiveness to methacholine were as strongly suppressed as after a short interval. These suppressive effects coincided with significantly reduced serum ovalbumin-specific IgE levels and T(H)2 cytokine production. On immunotherapy, the IL-5:IL-10 ratio in the bronchoalveolar lavage fluid shifted toward IL-10. In ovalbumin-restimulated lung cell and thoracic lymph node cultures from these mice, IL-5 levels dramatically decreased, whereas the percentage of IL-10(+)CD4(+) T cells was not affected. Finally, in mice treated with mAb against IL-10 receptors, the beneficial effects of immunotherapy were largely abrogated. CONCLUSION: These data demonstrate that allergen immunotherapy induces a memory suppressive effect in which IL-10 is essential.     

Reversibility of structural changes in chromatin of interphase nuclei of peripheral blood lymphocytes of patients with Down's syndrome under the influence of healthy human serum

A luminescence-microscopic investigation of short-term human cell cultures stained with Acridine Orange showed that the melting curve of the cell chromatin DNA in the region from 78 to 85°C depends on changing external environmental conditions, i.e., on the composition of the blood serum.Presented by Academician of the Academy of Medical Sciences of the USSR N. A. Yudaev.Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 82, No. 7, pp. 878–879, July, 1976.     

神经营养素受体在人外周血T细胞中表达的研究

目的 研究人外周血CD4^ /CD8^ T细胞4种神经营养素受体基因的转录。方法 应用尼龙手法分离出T细胞，磁式细胞分离法（MACS）分离CD4^ /CD8^ T细胞亚群，再以RT－PCR法研究4种神经营养素受体在两种T细胞亚群上的表达。结果 未经刺激的CD4^ /CD8^ T细胞亚群不表达任何神经营养素受体。经PHA或PPD刺激后，CD4^ /CD8^ T细胞亚群表达trkA,CD8^ T细胞亚群表达trkC；而在各种状态下的T细胞上均未见表达trkB及p75^NGFR。结论神经营养素受体在两种T细胞亚群中有不同的表达格局，提示不同T细胞亚群受神经营养素调节的模式可能各不相同。