Clonal expansion of myelin basic protein-reactive T cells in patients with multiple sclerosis: Restricted T cell receptor V gene rearrangements and CDR3 sequence

Myelin basic protein (MBP)-reactive T cells are thought to play an important role in the pathogenesis of multiple sclerosis (MS). In some patients with MS, these autoreactive T cells display a limited heterogeneity in their epitope recognition and T cell receptor (TCR) variable (V) gene usage. These individual-dependent properties of MBP-reactive T cells have led to the speculation that they may represent clonal expansion in vivo in some MS patients. In the present study, 51 MBP-reactive T cell clones derived from patients with MS and healthy individuals were examined for their epitope recognition and the TCR Vα and Vβ gene rearrangements. The V gene junctional region sequences of identified α and β genes were further analyzed to probe their clonal origins, as the sequences are unique for individual clones. Our data showed that 26 clones derived from nine patients with MS shared a predominant reactivity to the immunodominant regions of MBP, 84–102, 110–129 and 143–168, and used various TCR Vα and Vβ rearrangements. The V gene usage of the clones was restricted to certain Vα Vβ combination(s) in a given MS patient, but varied among different patients. The sequence analysis revealed that the clones generated from a given patient shared a limited or a single junctional region sequence pattern(s), indicating their oligoclonal or monoclonal origin(s). In contrast, 25 MBP-reactive T cell clones derived from normal individuals exhibited unfocused epitope recognition and V gene usage. Thus, the limited heterogeneity of MBP-reactive T cells in their structural and functional charactertistics reflects their clonal expansion in vivo in some patients with MS.     

EB病毒感染与中线恶性网织细胞增多症

使用一个针对ＥＢ病毒编码的小分子ＲＮＡ（ＥＢＥＲ）的寡核苷酸探针对１９例中线恶性网织细胞增多症病变组织进行了原位杂交检测，并配合免疫表型分析。结果为：（１）本组病例中１８／１９例（９４．７％）的病变组织中的异形淋巴样细胞表达Ｔ细胞分化抗原。ＣＤ３阳性１５例，ＵＣＨＬ１阳性９例，其中二者均阳性６例，但各例中的异形淋巴样细胞均未表达Ｂ细胞及组织细胞分化抗原；（２）ＥＢＥＲ原位杂交检测的阳性数高（１５／     

The hand-foot-genital syndrome: on the variable expression in affected males

Fryns JP, Vogels A, Decock P, Van den Berghe H. The hand-foot-genital syndrome: on the variable expression in affected males.
Clin Genet 1993: 43: 232–234. © Munksgaard, 1993
In this report we document male-to-male transmission in the hand-foot-genital syndrome. An affected father transmitted the syndrome to his three sons. A grade IV hypospadias, which was the most severe genital anomaly in affected males, was present in the youngest, moderately mentally retarded microcephalic male sibling.     

Author index for Volume 121, Number 1

Transformation of primary rat kidney cells with specific genome fragments of oncogenic human adenovirus type 12 provides a suitable model for the study of separate phenotypic manifestations of (tumorigenic) transformation. In this model, oncogenic transformation by specific virus fragments was accompanied by the appearance of a new, high-molecular-weight class of glycoprotein-bound carbohydrates similar as observed in a variety of spontaneous and experimental tumors. These tumor-associated carbohydrate changes were absent on the surface of nontumorigenic cells, morphologically transformed by other Ad 12 genome fragments or on untransformed control cells. It is concluded that tumor-associated changes in membrane carbohydrates are expressed simultaneously with a 60kD T antigen required for oncogenicity. These changes in carbohydrate composition can be distinguished from those induced by morphological transformation and growth per se.     

Zur Chromosomen-Replikation in Zellen der chronischen myeloischen Leukämie

Zusammenfassung Späte Replikation an Chromosomen von Blut- oder Knochenmarkszellen mit Philadelphia-Chromosom von Kranken mit CML wurde in 6 Fällen autoradiographisch untersucht und mit Befunden an normalen kultivierten Lymphocyten verglichen.1. Mitosen von Leukämiezellen fanden sich erst nach relativ langer Anwesenheit von³H-Thymidin markiert, woraus sich für Zellen der CML eine längere G₂-Phase als für kultivierte Lymphocyten ergab.2. Das Philadelphia-Chromosom wich in den meisten Zellen nicht wesentlich von den übrigen Chromosomen Nr. 21 und 22 ab und war autoradiographisch nicht sicher einem der beiden Paare zuzuordnen, in dem es zum Teil stärker mit dem spätreplizierenden und ebenso häufig mit dem früher replizierenden G-Chromosomenpaar übereinstimmte.3. Wie in der Lymphocytenkultur waren charakteristische Regionen der Autosomen Nr. 3–5 und 13–15 spät replizierend, wobei die Homologen weitgehend übereinstimmten.4. Feine Unterschiede in der Lokalisation der spätreplizierenden Zonen bzw. der maximalen Markierung gegenüber kultivierten Lymphocyten zeigten die Chromosomen Nr. 1 und 2. Diese Eigentümlichkeit wird im Hinblick auf die Auflösungsfähigkeit der Methode, die Spezifität hämatopoetischer Zellen des Knochenmarks und leukämisch entarteter Zellen im einzelnen besprochen.

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Chromosome replication in chronic myelocytic leukemia cells

Summary Late replication in chromosomes from blood or bone marrow cells with the Philadelphia chromosome from patients with chronic myelocytic leukemia (CML) was studied autoradiographically in 6 cases. These observations were compared with the findings in normal cultivated lymphocytes. (1) Mitoses of leukemia cells were only found to be labelled after relatively long presence of³H-thymidine. Consequently, the G₂ phase was longer for CML cells than for cultured lymphocytes. (2) In most instances the Philadelphia chromosome did not differ from the other chromosomes number 21 and 22. Autoradiographically it could not be classified as one of the two pairs. In the same number of cells this chromosome had a similar replication pattern compared to the later or the earlier replicating pair. (3) As in lymphocyte cultures, the characteristic regions of the autosomes number 3 to 5 and 13 to 15 were late replicating; in these instances the homologous autosomes were quite similar. (4) The chromosomes number 1 and 2 showed slight differences in the localization of late replicating areas or the highest labelling as compared to cultivated lymphocytes. These properties are discussed in detail as to the sensitivity of the method used, the specificity of haemopoietic cells of bone marrow and leukemia cells.

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Mit Unterstützung der Deutschen Forschungsgemeinschaft.     

A duplication/paracentric inversion associated with familial X-linked deafness (DFN3) suggests the presence of a regulatory element more than 400 kb upstream of the POU3F4 gene

X-linked deafness with stapes fixation (DFN3) is caused by mutationsin the POU3F4 gene at Xq21.1. By employing pulsed field gelelectrophoresis (PFGE) we identified a chromosomal aberrationin the DNA of a DFN3 patient who did not show alterations inthe open reading frame (ORF) of POU3F4. Southern blot analysisindicated that a DNA segment of 150 kb, located 170 kb proximalto the POU3F4 gene, was duplicated. Fluorescence in situ hybridization(FISH) analysis, PFGE, and detailed Southern analysis revealedthat this duplication is part of a more complex rearrangementincluding a paracentric inversion involving the Xq21.1 region,and presumably the Xq21.3 region. Since at least two DFN3-associatedminideletions are situated proximal to the duplicated segment,the inversion most likely disconnects the POU3F4 gene from aregulatory element which is located at a distance of at least400 kb upstream of the POU3F4 gene.     

Non-lymphoid and lymphoid cells in acute, chronic and relapsing experimental colitis.

In rodents, intracolonic administration of ethanol 30% induces an acute colitis, while administration of 2,4,6-trinitrobenzene sulphonic acid (TNBS) in ethanol induces a longer lasting colitis. In the acute and chronic stages of experimental colitis, lymphoid and non-lymphoid cells were studied in the colon by immunohistochemistry. During the acute inflammation a high damage score of the colon was observed, which was related to an increase in the number of macrophages and granulocytes. Also a change in distributional patterns of macrophage subpopulations was found. The chronic stage of TNBS-ethanol-induced colitis was characterized by an increase in the number of lymphocytes, especially T cells. These data suggest that macrophages and granulocytes are important in the acute phase of experimental colitis, while lymphocytes play a pivotal role in the chronic stage. As most inflammatory bowel disease (IBD) patients have relapses during the chronic disease, we attempted to induce a relapse during experimental colitis by giving a second i.p. or s.c. dose of TNBS. This resulted in increased damage scores of the colon, new areas of ulceration and a further increase in macrophage numbers. No effect on the number of granulocytes was seen. These results indicate that it is possible to mimic relapses in experimental colitis by a second administration of TNBS, and suggest that the rats had been sensitized by the first dose of TNBS, given into the colon.     

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