Antigen-induced tolerance by intrathymic modulation of self-recognizing inhibitory receptors

CD1d-restricted invariant natural killer T cell (iNKT cells) have a limited T cell receptor (TCR) repertoire and share characteristics common to T cells and natural killer cells. While intrathymic selection facilitates the production of T cells carrying self major histocompatibility complex-restricted TCRs, natural killer cells carry an appropriate repertoire of self major histocompatibility complex-recognizing receptors to avoid self-reactivity. Here we show that chronic exposure to specific glycolipid antigen resulted in iNKT cell disappearance and thymus-dependent repopulation of iNKT cells with increased expression of inhibitory Ly-49 molecules that resulted in impaired responsiveness. Thymic selection of peripheral Ly-49-expressing iNKT cell repertoire inhibited cytokine production and other functions in vivo. These observations emphasize the acquisition of self-recognizing inhibitory receptors on NKT cells as a previously unknown mechanism of thymic tolerance after chronic antigen exposure.     

T cell developmental defects in 'viable motheaten' mice deficient in SHP-1 protein-tyrosine phosphatase. Developmental defects are corrected in vitro in the presence of normal hematopoietic-origin stromal cells and in vivo by exogenous IL-7

Defects in the gene that encodes SHP-1 protein tyrosine phosphatase result in multiple hematopoietic abnormalities and generalized autoimmunity in viable motheaten (me(v)) mice. These mice also exhibit early thymic involution and abnormalities in T cell development. Here, we describe the use of fetal thymic organ culture (FTOC) and bone marrow adoptive transfer to study the effects of SHP-1 deficiency on thymocyte development. Chimeric FTOC established with normal bone marrow placed onto deoxyguanosine-treated fetal thymic lobes or onto scid fetal thymic lobes generated T cells. Bone marrow from SHP-1-deficient me(v)/ me(v) mice generated decreased numbers of T cells in chimeric FTOC established using deoxyguanosine-treated thymi but generated normal numbers in chimeric FTOC established using scid thymi. However, scid fetal thymi seeded with me(v)/ me(v) bone marrow also exhibited morphological abnormalities and contained elevated numbers of macrophages. Addition of IL-7 to me(v)/ me(v) bone marrow-seeded scid FTOC led to increased cell numbers, particularly of macrophages. Intrathymic injection of IL-7 partially restored the ability of progenitor cells in me(v)/ me(v) bone marrow to populate the thymus of adoptive recipients. We conclude that abnormal T cell development in me(v)/ me(v) mice may in part be due to defects in the ability of bone marrow-derived accessory cells to provide bioavailable IL-7 to developing thymocytes.     

太空发育鸡胚的前庭感受器细胞形态学研究

为了探讨太空微重力对鸡胚前庭感觉上皮细胞的形态发育的影响 ,选取在航天飞机 (STS-2 9)发育鸡胚和地面发育鸡胚各两只 ,利用计算机显微测量技术分别测量椭圆囊和球囊的毛细胞、支持细胞核的切面面积、周长、形状系数。太空发育鸡胚的球囊支持细胞核的切面面积、周长显著大于地面组 ,形状系数无差异 ;太空发育鸡胚的椭圆囊支持细胞核的切面面积、周长、形状系数以及椭圆囊和球囊毛细胞的切面面积、周长与地面发育鸡胚相比无明显差异。微重力可能对球囊支持细胞核的体积发育有影响 ,对椭圆囊和球囊的毛细胞以及椭圆囊支持细胞核的形态发育无影响。     

Plasticity of the medial prefrontal cortex: Facilitated acquisition of intracranial self-stimulation by pretraining stimulation

Prior electrical stimulation of the medial prefrontal cortex MFC facilitated the subsequent acquisition of intracranial self-stimulation (ICSS) from the same MFC electrode site. Stimulations that were spaced over a period of six days were more effective in producing this facilitation than the same number of stimulations delivered over a two day period. These data suggest that the rewarding effects of MFC stimulation may involve some process akin to the kindling phenomenon and as such may provide insights in the neuronal modifications thought to underlie learning and memory.     

Dielectrophoretic assay of bacterial resistance to antibiotics

The dielectrophoretic collection spectra of antibiotic-sensitive and antibiotic-resistant strains of Staphylococcus epidermidis have been determined. These indicate that in the absence of antibiotic treatment there is a strong similarity between the dielectric properties of sensitive and resistant strains, and that there is a significant difference between the sensitive strains before and after treatment with the antibiotic streptomycin after 24 h exposure. This method offers possibilities for the assessment of bacterial resistance to antibiotics.     

Distribution of a formalin-resistant myelomonocytic antigen (L1) in human tissues. II. Normal and aberrant occurrence in various epithelia

L1 is an approximately 36-kd protein present in virtually all resting peripheral blood neutrophils and monocytes. It is particularly well preserved in formalin-fixed and paraffin-embedded routine material. In a recent immunohistochemical study, the authors showed that L1 has a restricted distribution within the monocyte-derived cell lineage, being mainly confined to reactive histiocytes (infiltrating macrophages). A protein sharing physicochemical and antigenic properties with L1 was identified in extracts of epidermal scales obtained from patients with psoriasis. This epithelial L1 was generally not expressed by normal epidermis, but its production was abundant in several skin diseases. Moreover, mucosal squamous epithelium normally expressed L1. No other epithelia showed signs of L1 production, although occasional patchy uptake was indicated, particularly in kidney tubular epithelium.     

CORTICAL SLOW POTENTIAL CHANGES IN MAN RELATED TO INTERSTIMULUS INTERVAL AND TO PRE TRIAL PREDICTION OF INTERSTIMULUS INTERVAL

Two experiments were performed to explore further the relationship between the cortical slow potential change known as the “contingent negative variation” (CNV) and the concept of “expectancy.” In Experiment I, 24 male Ss were presented click pairs, with inter-click intervals of 800, 1600 and 4800 msec (2 blocks of 10 trials each, counterbalanced between Ss for order), and instructed to press a key after the second click. Interval by order by trials analysis of variance showed interval to be the only significant factor: CNVs were lower and RTs longer as interval increased. In Experiment II, 8 female Ss given 60 pairs of clicks, 30 each with separations of 1200 and 2400 msec, were instructed to respond as in Experiment I, and were asked to make a pretrial prediction of the interval they would next receive. Analysis of variance of RTs showed that Ss responded slower when the interval was other than that predicted. Prediction by reception by subjects analysis of variance of CNV amplitude at the 1200 msec point gave a significant F only for prediction, mean amplitude for short being higher than for long. A similar design applied to CNV amplitudes at both the 1200 and 2400 msec points when Ss received the long interval yielded a significant measurement point by interval predicted interaction; at the 1200 msec point, short predictions were followed by higher CNVs than were long predictions; at 2400 msec, the opposite was found. These data combine with those already in the literature to indicate that the relationship between “expectancy” and the CNV is far from simple, and that cognitive and motivational factors play a significant role in determining CNV amplitude.