摘要:

SummaryInfection of BALB/c mice with murine cytomegalovirus (MCMV) decreased the numbers of cells recovered from the thymus by 80–90% after 4–7 days, although less than 10 thymocytes per million were productively infected with the virus. A loss of cortical thymocytes was evident in histologic sections and correlated with depletion of CD4+CD8+cells.Thymic involution was minimal in C57BL/6 mice. This resistance was not H‐2b‐associated, as BALB.B (H‐2b) mice were severely affected. In CXB recombinant inbred mice, thymic involution and MCMV replication co‐segregated with atrophy and infection of the spleen and bone marrow. This suggests common regulation by natural killer (NK)1.1+cells, consistent with the enhanced thymic involution demonstrated in NK‐deficient bg/bg mice. However, CD4−CD8−cells were not depleted, so bone marrow hypoplasia may not be the proximal cause of thymic involution.MCMV infection activated CD4+, CD8+and CD4+CD8+thymocytes, as expression of MEL14, major histocompatibility complex class I (H‐2) and Sca‐1 antigens increased on these cells.In vitrolymphoproliferation and interleukin (IL)‐3 release were enhanced in unseparated and CD4+‐enriched thymus preparations. Maturation of the thymus population was also evident from the high frequencies of single positive CD4+and CD8+cells and the decline in Sca‐2 expression. However, unlike peripheral T cells, thymocytes from infected mice did not release IL‐2. The results suggest that thymic involution accelerates the transit of cells through the thymus. The possibility that this impairs the elimination of autoreactive T cells within the thymus and promotes the autoimmune manifestations of MCMV disease is discussed.

ISSN:0004-945X    

DOI:10.1038/icb.1993.18

出版商:Blackwell Publishing Ltd    

年代:2017

数据来源: WILEY

摘要:

SummaryTumour cell heterogeneity is probably a principal cause of treatment failure and represents a formidable barrier for effective antibody‐targeted chemotherapy. Idarubicin (Ida), a more potent and less cardiotoxic analogue of daunomycin, has been demonstrated to specifically target and eradicate homogeneous, cloned, murine tumour cell populationsin vitroandin vivowhen coupled to monoclonal antibodies (MoAb); however, the antitumour activity of Ida‐MoAb conjugates against human tumour xenografts remains to be established. In this study, the value of cotargeting conjugates to different human tumour‐associated antigens within a solid tumour has been assessed by comparing the effects of combinations of Ida‐anti‐colon carcinoma MoAb conjugates with any one Ida‐anti‐colon carcinoma MoAb conjugate used alone. Individual Ida‐MoAb conjugates have previously been evaluated for their specific binding and cytotoxicity to one of two different human colon carcinoma xenografts (Colo 205 or LIM2210)in vitro, although their efficacy alone or in combination required assessmentin vivo.Combinations of the most effective Ida‐MoAb conjugates were demonstrated to enable a greater number of complete tumour regressions than the most efficacious Ida‐MoAb conjugate administered alonein vivo; some combinations inhibited control tumour growth by up to 95%. This study suggests that Ida‐MoAb conjugates can be effective against subcutaneous human tumours in nude mice, although it is unlikely that any single conjugate will eradicate all the tumour cells in a solid tumour, and the value of ‘cocktails’ of drug‐MoAb conjugates against some xenografts (i.e. LIM2210) appears to be limited.

ISSN:0004-945X    

DOI:10.1038/icb.1993.19

出版商:Blackwell Publishing Ltd    

年代:2017

数据来源: WILEY

摘要:

SummaryThe inhibitory effect of glycyrrhizin (GR), an anti‐inflammatory Chinese herbal drug extracted from licorice roots, on the generation of suppressor T cells in thermally injured mice (TI‐mice) was investigated. The burn‐associated suppressor T cell (BTs cell) activity was demonstrated in splenic mononuclear cells (SMNC) from mice 2 to 8 days after thermal injury when suppressor cell activity was assayed in a one‐way mixed lymphocyte reaction. However, when TI‐mice were treated with GR, SMNC harvested 6 days after thermal injury showed no suppressor cell activity. This activity of GR demonstrated a dose‐response effect, with a dose of 10 mg/kg exhibiting peak levels of the activity. Since GR had no direct inactivating activities against BTs cellsin vitro, the inhibitory effect of SMNC, derived from TI‐mice treated with GR, on the activity of BTs cells was examined in the same mixed lymphocyte reaction system, and the results showed that the SMNC from GR‐treated mice 6 days after thermal injury counteracted the activity of BTs cells. The type of cell responsible for this inhibition of BTs cell activities was a CD3+, L3T4+,Vicia villosalectin‐adherent T cell with the same phenotypic properties previously exhibited by contrasuppressor cells. These results suggest that GR may regulate the generation of BTs cells through the induction of contrasuppressor cells. Since there are many reports describing septic infections due to the appearance of BTs cells in postburn patients, it may be possible to apply GR or blood preparations containing contrasuppressor cell populations induced by GR in healthy volunteers into immunosuppressed burn patients to avoid infections.

ISSN:0004-945X    

DOI:10.1038/icb.1993.20

出版商:Blackwell Publishing Ltd    

年代:2017

数据来源: WILEY

摘要:

SummaryThe early development of the parietal cell in the embryonic murine gastric mucosa was investigated with particular attention paid to the biogenesis of the secretory membranes and the localization of the gastric H+/K+/ ATPase α and β subunits. Gastric glands were recognized in the day 18 foetus. However, at this stage in development no parietal cells could be distinguished ultrastructurally in the glands, and no immunoreactivity was detected with monoclonal antibodies to either the α or β subunits of the gastric H+/K+ATPase. In the 19 day embryo, parietal cells were recognizable morphologically by the presence of slender microvilli on the apical (lumenal) surface and differentiating intracellular canaliculi in the apical cytoplasm. Both subunits of the proton pump were found to be specifically associated with the apical and canalicular membranes and with the membranes of relatively large vesicles distributed in the subapical cytoplasm and the cytoplasm surrounding the canaliculi. In the parietal cells of the day 1 neonate, the intracellular canaliculi had extended basally to form the extensive compartments typical of parietal cells in the adult animal. Again, profiles of vesicles showing H+/K+ATPase immunoreactivity were present in the pericanalicular cytoplasm. These results indicate that the intracellular canaliculi are formed by expansion of the apical surface and suggest that the delivery of newly synthesized gastric H+/K+ATPase α and β subunits to the apical plasma membrane is mediated by typical Golgi transport vesicles. The large immunoreactive vesicles that occur in the apical and pericanalicular cytoplasm of the developing cells may represent artifacts generated by fixation‐induced fragmentation of the differentiating canalicular membrane system during preparation.

ISSN:0004-945X    

DOI:10.1038/icb.1993.21

出版商:Blackwell Publishing Ltd    

年代:2017

数据来源: WILEY

摘要:

SummaryThe vectorial secretion of the contents of highly specialized cytoplasmic granules is of pivotal importance to the killing by cytotoxic T cells and natural killer cells. The purification and biochemical characterization of some of the granule constituents, in particular the pore‐forming protein perforin, had engendered the notion that the killing of cellular targets was largely an osmotic phenomenon analogous to the insult delivered by complement attack. However, the apparent absence of membrane perforation in various examples of lymphocyte‐mediated killing, and the observation that perforation alone could not account for apoptosis associated with programmed cell death, suggested that perforin activity represented, at best, only a part of the whole mechanism. More recently, the characterization of a large family of granule serine proteases (granzymes) has provided evidence that these molecules may collaborate in the killing process by inducing a ‘suicide’ pathway in target cells, resulting in DNA fragmentation. However, the serine proteases are inactive alone, their natural substrates have not been defined and they require access into the target cell cytoplasm via perforin‐induced pores to exert their deleterious effects. Thus, we propose that the cytotoxic granule‐mediated mechanism comprises at least two interdependent arms, perforin and serine proteases, that together are capable of inflicting cell death by osmotic shock and/or nuclear collapse.

ISSN:0004-945X    

DOI:10.1038/icb.1993.22

出版商:Blackwell Publishing Ltd    

年代:2017

数据来源: WILEY

摘要:

SummaryTwo signal models for lymphocyte activation build on the Talmage/Burnet concept that receptor diversity is generated within the immune system by a random process, and that individual lymphocytes carry a single receptor on their surface that determines their specificity. Such models cannot use a concept of signal one anergy (or deletion) to explain the maintenance of self‐tolerance in terms of the Bretscher/Cohn theory if they abandon the concept of associative recognition.

ISSN:0004-945X    

DOI:10.1038/icb.1993.23

出版商:Blackwell Publishing Ltd    

年代:2017

数据来源: WILEY

摘要:

SummaryMosaic proteins consist of a group of proteins that may be comprised of one or more types of a variety of different structural modules and have a diverse range of functions. We have examined primary human astrocyte cultures for the presence of three mosaic proteins, B2I and the complement proteins factor H and properdin. Using the polymerase chain reaction and an enhanced chemiluminescence detection technique, we were able to show that mRNA transcripts for each of these proteins are expressed in human astrocytes.

ISSN:0004-945X    

DOI:10.1038/icb.1993.24

出版商:Blackwell Publishing Ltd    

年代:2017

数据来源: WILEY

摘要:

SummaryCandida albicansinfections were established in eight inbred strains of mice. Using established histological criteria, only two strains (AKR and CBA/CaH) were found to exhibit severe lesions. The remainder showed only mild tissue damage. Deaths occurred in three strains: CBA/CaH, A/J and DBA/2. The last two strains lack the important complement component C5. Colony counts in the brain varied widely between strains and showed no correlation with the extent or severity of tissue destruction. However, strains lacking C5 had a significantly greater fungal burden in the brain than C5‐sufficient mice. The data are discussed in relation to concepts of susceptibility and resistance toC. albicansin experimental infections in mice.

ISSN:0004-945X    

DOI:10.1038/icb.1993.25

出版商:Blackwell Publishing Ltd    

年代:2017

数据来源: WILEY

摘要:

SummaryThe distribution of nucleotide variability within and upstream of germ‐line VH186.2‐related variable genes was studied. The data in this report of work in progress indicate non‐random selection for variability in the second antigen‐contact or complementarity‐determining region (CDR2) for 12 such genes isolated using the polymerase chain reaction (PCR) technique from genomic C57BL/6 mouse liver DNA. The translated protein sequences of these and three additional previously published genes also display a pronounced Wu‐Kabat peak of amino acid variability in CDR2. In the CDR1 and CDR2 regions of this set of related germ‐line genes, there are no silent nucleotide changes, and most amino acid replacements (or non‐synonymous changes) are non‐conservative. In contrast, there is selection against amino acid replacements in the framework regions (FW), as indicated by the significant number of silent (or synonymous) mutational changes from the VH186.2 reference sequence. This is surprisingly similar to the Wu‐Kabat variability patterns observed in somatically mutated immune response antibodies. These data could imply similar diversification mechanisms acting on B cell‐expressed V genes in the soma (i.e. in a germinal centre) and in the germ‐line DNA of male and/or female germ cells. While always possible, we consider this unlikely. Similarly, we consider as unlikely an explanation based on a classical Darwinian model involving simple stepwise whole animal selection prior to reproduction for each VHand VLgene now phylogenetically stored in the V segment arrays of the genomic DNA. A more reasonable hypothesis for the origin and maintenance of the many germ‐line V genes would propose that there is a yet to be defined process providing a direct genetic link between somatically mutated and selected V genes and the germ‐line DNA repertoire.

ISSN:0004-945X    

DOI:10.1038/icb.1993.26

出版商:Blackwell Publishing Ltd    

年代:2017

数据来源: WILEY

摘要:

Book Reviewed in this articleSYSTEMIC AUTOIMMUNITY Edited by Pierluigi E. Bigazzi and Morris Reichlin.MEDIATORS OF PULMONARY INFLAMMATION Edited by Michael A. Bray and Wayne H.MICROBIAL PHYSIOLOGY I.W. Dawes and I.W.MICROBES AND MAN By John Postgate.E. V. KEOGH. SOLDIER, SCIENTIST AND ADMINISTRATOR By Lyndsay Gardiner.

ISSN:0004-945X    

DOI:10.1038/icb.1993.27

出版商:Blackwell Publishing Ltd    

年代:2017

数据来源: WILEY