bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autoantibodies against cyclophilin in systemic lupus erythematosus and Lyme disease
Authors: KRATZ A , HARDING M W , CRAFT J , MACKWORTH-YOUNG C G , HANDSCHUMACHER R E 
Published: July 2010

SUMMARY
Autoantibodies against cyclophilin, a cyclosporin A binding protein, were detected in sera of 29 of 46 (63%) patients with systemic lupus erythematosus and 14 of 40 (35%) Lyme disease patients. The antibodies are directed against the denatured form of both the major and minor isoform of cyclophilin and, can be demonstrated in Western blots. Some first-degree relatives of lupus patients also express these antibodies. They are specific for cyclophilin and are not the consequence of hypergammaglobulinaetnia. Four monoclonal IgM antibodies from a patient with lepromatous leprosy also bound to cyclophilin. The generation of these antibodies may be of special interest because they are against a protein involved in the control of the immune system not known to be directly associated with DNA or RNA.
Idiotypic mimicry of a cell surface DNA receptor: evidence for anti-DNA antibodies being a subset of anti-anti-DNA receptor antibodies
Authors: BENNETT R M , CORNELL K A , MERRITT M J , BAKKE A C , MOURICH D , HEFENEIDER S H 
Published: July 2010

SUMMARYAnti-idiotypic anti-DNA antibodies (anti-anti-DNA) have previously been described in both patients with systemic lupus erythematosus and healthy individuals. Jerne's hypothesis predicts that such antibodies would bear a paratope reactive with non-sequence specific DNA binding proteins. Here we have explored the notion of a molecular mimicry between anli-anti-DNA antibodies and antibodies to a previously described 28–29 kD cell surface DNA binding molecule. It was shown that affinity purified anti-anti-DNA antibodies inhibit the binding of DNA to cells and that MoAb to the 28–29 kD receptor react with anti-DNA antibodies. These findings indicate that a subset of anti-anti-DNA antibodies are idiotypically related to antibodies reactive with a cell surface DNA binding molecule. It is hypothesized that anti-DNA antibodies may arise when a convergence of genetic and environmental influences favours an unrestrained anti-idiotypic response to cell surface DNA binding molecule(s).
In vitropreacdvated human T cells engraft in SCID mice and migrate to murine lymphoid tissues
Authors: ARMSTRONG N , CIGEL F , BORCHERDING W , HONG R , MALKOVSKA V 
Published: July 2010

SUMMARYMice with severe combined immunodeficiency (SCID) accept grafts of human T and B lymphocytes derived from resting peripheral blood mononuclear cells (PBMC). We wished to determine whether activated human T cells engraft and migrate into lymphoid tissues in SCID mice. PBMC (50 × 106) activated in vitro in a 4-day mixed lymphocyte culture (MLC) were injected into the peritoneum of 12 SCID mice. In 11 of 12 animals killed at 3 or 4 weeks after injection, human cells were detected in cells pooled from lymphoid organs by flow cylomctry and by immunohistochemical staining of frozen tissue sections. The percentage of CD45+ cells in the 11 mice ranged from 2% to 45% and the absolute numbers of CD45+ cells recovered from lymphoid organs ranged from 4 × 106 to 90 × 106. Up to 93% of the human cells expressed the CD3 antigen together with either CD4 or CDS. Human T cells were localized in periarteriolar areas in murine spleens, whereas in the lymph nodes and gut mucosa, the T cells did not show the pattern for T-dependcnt areas found in human lymphoid tissue. Numerous human plasma cells were detected in the spleen and gut mucosal crypts of engrafted SCID mice. Human IgG was delected in the serum of all 11 engrafted SCID mice. The functional activity of human T cells recovered from murine splenic tissue was very low 3–4 weeks after engraftment.
An early defect in primary and secondary T cell responses in asymptomatic cats during acute feline immunodeficiency virus (FIV) infection
Authors: BISHOP S A , WILLIAMS N A , GRUFFYDD-JONES T J , HARBOUR D A , STOKES C R 
Published: July 2010

SUMMARYAs in HIV infection of humans, cats infected with FIV are particularly susceptible to secondary infection by opportunistic pathogens, suggesting an impaired ability to elicit an effective immune response against foreign antigens. In order to investigate the development of immunity in FIV-infected cats, we have used an autologous culture system to directly measure priming of naive CD4+ T cells to soluble protein antigen, in vitro. Using this assay, we showed previously that cats infected with FIV for several months had significantly reduced primary proliferative responses. We have now examined cats before infection, and at varying times after infection with FIV, to determine how soon after infection this defect in T cell priming was evident, compared with other quantitative and qualitative measurements of lymphocyte function. Our results showed a progressive decline in immune function in asymptomatic cats during the acute stage of infection with FIV. Primary T cell responses were most sensitive and a significant reduction in proliferation of naive T cells to foreign antigen occurred 5 weeks after infection, despite normal blastogenesis to T cell mitogens and normal CD4+/CD8+ ratios at these times. Whilst lymphocyte proliferation to T cell mitogens was unaffected throughout, a significant reduction in proliferation to a B cell milogen occurred from week 8 onwards. CD4+/CD8+ ratios fell significantly from week 13 onwards, and proliferation of the memory T cell population to a recall antigen was significantly impaired later, from week 19 onwards. The defect in the priming of naive T cells to foreign antigen early after infection may be important in determining susceptibility to secondary infections.
Haemorrhage-induced alterations in function and cytokine production of T cells and T cell subpopulations
Authors: ABRAHAM E , CHANG Y-H 
Published: July 2010

SUMMARYHaemorrhage produces alterations in macrophage, T and B cell function. In order to better define the mechanism for the effects of blood loss on immune response, we examined function of and cytokine production by purified T cells, CD4+ and CD8+ subpopulations after blood loss. Whereas T and CD4+ cells from control, unhaemorrhaged animals produced no alteration in proliferation when added to cultures of mitogen-stimulated splenocytes from normal mice, proliferation was decreased when T or CD4+ cells from haemorrhaged mice were included. The addition of CD8+ cells from haemorrhaged animals to mitogen-stimulated cultures reduced proliferation by approximately 50% more than that found when CD8+ cells from control, unhaemorrhaged animals were included. Supernatants of mitogen-stimulated splenocytes from haemorrhaged mice contained significantly less IL-2 and interferon-gamma (IFN-γ) than did those from control, unhaemorrhaged mice. CD4+ populations from haemorrhaged mice produced significantly more IL-10, and significantly less IFN-γ, than did CD4+ cells from control, unhaemorrhaged mice. There were no significant differences in IL-2, IL-4, IL-10 or IFN-γ production by CD8+ cells from haemorrhaged or control mice. The present experiments demonstrate that haemorrhage affects both CD4+ and CD8+ T cell subsets. In particular, haemorrhage appeared to activate CD4+, Th2 cells, with concomitant suppression of the Thl subpopulation. These results provide a mechanism which may contribute to the alterations in cytokine production previously described to occur following blood loss.
Distribution of the PBC-specific- (M2) and the naturally-occurring mitochondrial antigen- (NOMAg) systems in plants
Authors: LANG P , KLEIN R , BECKER E W , BERG P A 
Published: July 2010

SUMMARY
In previous studies it was demonstrated that antibodies in sera from patients with primary biliary cirrhosis (PBC) and their relatives can recognize two different antigen systems in the ATPase fraction prepared from beef heart mitochondria, namely the PBC-related M2- and the naturally occurring mitochondrial antigen (NOMAg)-relatcd epitopcs. Since separation of these two antigen systems could not be achieved using mammalian mitochondria, mitochondria from a wide spectrum of plants were analysed with respect to the presence of mitochondrial antigens. Mitochondria from 29 species of plants were prepared and tested by ELISA and Western blot using marker sera from patients with PBC reacting in the Western blot with M2a,b,c,d (alpha-ketoacid-dehydrogenase complex) and NOMAg-specificsera recognizing the three majorepitopes cpsilon, zeta. and eta at 65,61 and 58 kD. Naturally occurring mitochondrial antibody (NOMA)-positive marker sera reacted in the ELISA with mitochondria from all plants, and the zeta/eta positive sera gave also a positive reaction at 61/58 kD in the Western blot while the epsilon epitope could not be visualized by this method. In contrast, the M2 antigen was detected preferentially in lower plants such as algae, fungi, and ferns. Analysing these data with respect to the evolution of proteins one would have to assume that the M2 antigen was lost in most higher plants or underwent some structural alterations. Furthermore, considering the fact that the M2- and the NOMAg-relatcd epitopcs could be only partially separated, i.e. there were no plant mitochondria showing only M2 but no NOMAg, one could speculate that anti-M2 antibodies are derived from the pool of naturally occurring antibodies.
Gene frequency and partial protein characterization of an allelic variant of mannan binding protein associated with low serum concentrations
Authors: GARRED P , THIEL S , MADSEN H O , RYDER L P , JENSENIUS J C , SVEJGAARD A 
Published: July 2010

SUMMARYLow plasma concentration of mannan binding protein (MBP) has been shown to be the basis for a common opsonic deficiency and suggested to be caused by a single nucleotide substitution at base 230 of exon 1 in the MBP gene. This substitution causes a replacement of glycine (codon GGC) with aspartic acid (codon GAC). Of 123 healthy Danish individuals investigated by polymerase chain reaction performed on exon 1, followed by restriction fragment length polymorphism or allospecific probing, 93 were homozygous (75.6%) for GGC, 28 heterozygous (22.8%), and two homozygous for GAC (1.6%). The gene frequency of the GAC allele was found to be 013. DNA sequencing of the cloned exon 1 from one GAC homozygous individual revealed no other substitution. The median MBP concentration in the group containing the GAC allele was 6.4 times lower than in the GGC homozygous group (195 and 1234 μ/l respectively). However, the range in plasma concentrations of MBP was wide and overlapping between the groups. MBP protein was detected in both the GAC homozygotes (9 and 387 μ/l. Furthermore, no difference in relative mass and biological activity (mannan binding) was found when sera containing the two forms of MBP were investigated. Accordingly, it can be concluded that the GAC allele is able to produce a functional MBP protein which may be detected in serum at low concentrations.
Bacterial lipopolysaccharide mediates the loss of CD4 from the surface of purified peripheral blood monocytes
Authors: NEATE E V , GREENHALGH A M , MRPHEE D A , CROWE S M 
Published: July 2010

SUMMARYIn this study we have looked at the effect of lipopolysaccharide (LPS) on the surface antigen expression of cultured monocytes. Monocytes were purified from peripheral blood mononuclcar cells (PBMC) and cultured in the presence or absence of LPS. The cultured cells were then stained with anti-MO3, anti-IL-2R and anli-CD4 MoAbs. We have shown that freshly isolated monocytes are IL-2R- and MO3-negative and express CD4 in low density. After overnight culture, without LPS, the expression of these surface markers remained relatively unchanged. However, in the presence of LPS (1 μg/ml) CD4 expression was reduced to undetectable levels while the expression of IL-2R and MO3 was induced to maximal density. This effect of LPS on monocyte surface antigen expression was demonstrated with LPS preparations from Escherichia coli. Salmonella typhi and Vibrio cholerae. Surface antigen expression after 7 days culture in medium supplemented with non-heat-inactivaled serum was essentially as seen after overnight culture, with the exception that LPS-induccd IL-2R expression was transient. The ability to prepare monocytes that maintained surface CD4 expression after overnight culture was donor dependent.
Enhancement of HIV-specific cytotoxic T lymphocyte responses by zidovudine (AZT) treatment
Authors: DADAGLIO G , MICHEL F , LANGLADE-DEMOYEN P , SANSONETTI P , CHEVRIER D , VUILLIER F , PLATA F , HOFFENBACH A 
Published: July 2010

SUMMARYZidovudine or 3′-azido-2′-3′-dideoxy-thymidine (AZT) is an antiviral drug widely used to treat HIV-infected patients. Because cytotoxic T lymphocytes (CTL) are thought to contribute actively to resistance against HIV-induced disease, we studied sequentially 10 HIV-infected individuals under zidovudine treatment for a period of 6–12 months. For a given patient all lymphocyte suspensions corresponding to the complete zidovudine therapy period were tested on the same day and on the same target cells. Patients were selected for expression of HLA-A2 and/or HLA-A3 class I transplantation antigen. HLA-restricted cytotoxicity specific for env, gag and nef HIV proteins was quantified for each patient at 6 week intervals. The data clearly indicated that zidovudine has a beneficial effect on the CTL response during the first 6–12 weeks of treatment, inducing cytotoxicity levels up to 100-fold stronger than base line. This effect was usually short lived. However, patients who maintained strong levels of cytotoxicity had better clinical and survival outlook than patients who had lost all detectable cytotoxic lymphocytes. It is proposed that AZT, among other effects, delays the onset of disease in HIV-infected patients by contributing to the stimulation of the HIV specific CTL response.
Contribution of non-Leishmania-specific immunity to resistance to Leishmania infection in humans
Authors: AKUFFO H O , BRITTON S F F 
Published: July 2010

SUMMARYLymphocytes of individuals from a country non-endemic for Leishmania (Sweden), responded with a vigorous interferon-gamma (IFN-γ) and IL-6 response when exposed to live or dead promastigotes of Leishmania aethiopica. This response was sometimes as strong as when the same cells were exposed to the mitogen (phytohaemagglutinin (PHA)). Furthermore, supernatants of cells exposed to Leishmania promastigotes were able to inhibit the amastigote form of the same parasite. In some few instances there was no such reactivity to Leishmania parasites. It is proposed that most individuals have such a first line cytokine response which is enough to prevent further spread and growth of the parasites. In exposed individuals who display disease symptoms, this non-Leishmania-specific response is overcome (by dose) or is weak (for genetic reasons). In the latter instances curbing of parasite growth would depend on acquired immunity.
Failure of Epstein-Barr virus-specific cytotoxic T lymphocytes to lyse B cells transformed with the B95-8 strain is mapped to an epitope that associates with the HLA-B8 antigen
Authors: MISKO I S , SCHMIDT C , HONEYMAN M , SOSZYNSKI T D , SCULLEY T B , BURROWS S R , MOSS D J , BURMAN K 
Published: July 2010

SUMMARYThere are two types, A and B, of Epstein-Barr virus (EBV) and B95-8 represents the common type A laboratory strain. Herein, we show in a family study that paternal EBV-specific cytotoxic T lymphocytes (CTL) generated in short-term cultures following stimulation with the autologous B95-8-transformed lymphoblastoid cell line (LCL) or B cells freshly infected with the B95-8 isolate did not lyse haploidentical B95-8 LCL expressing the HLA-A1-B8,-DR3 paternal haplotype. In contrast, the haploidentical B95-8 LCL expressing the HLA-A11,-B51,-DR7 paternal haplotype was strongly lysed. Moreover, paternal CTL generated in response to stimulation with the B95-8 LCL expressing the haploidentical HLA-A1,-B8, -DR3 paternal haplotype included an allogeneic response against the maternal haplotype but no EBV-specific response as shown by the poor lysis of the autologous LCL target cells. However, stimulation with the haploidentical HLA-A11,-B51, -DR7 paternal haplotype resulted in the generation of both an allogeneic and an EBV-specific response. CTL clones were generated from two HLA-B8+ donors in response to stimulation with the autologous type A LCL transformed with wildtype EBV. The clones were cross-reactive for an immunodominant B95-8-associalcd peptide epitope that interacted with the HLA-B8 allele but failed to lyse B95-8-transformed LCL largets unless the targets were pre-coated with the exogenous peptide. A CTL clone that was initially stimulated with the autologous BL74 LCL lysed the spontaneous autologous LCL and spontaneous LCL from an HLA-B8+ donor, but failed to lyse the B95-8 LCL from that donor. The observed haplotype preference can be explained in terms of sequence variation between the B95-8 and the corresponding wildtype epitope. Our findings may help to clarify the role of EBV in the pathogenesis of primary Sjögren's syndrome which is closely associated with HLA-B8.
Cell-mediated immunity in patients with chronic fatigue syndrome, healthy control subjects and patients with major depression
Authors: LLOYD A , HICKIE I , HICKIE C , DWYER J , WAKEFIELD D 
Published: July 2010

SUMMARYThe chronic fatigue syndrome (CFS) is characterized by severe persistent fatigue and neuropsychiatric symptoms. It has been proposed that the abnormalities in cell-mediated immunity which have been documented in patients with CFS may be attributable to a clinical depression, prevalent in patients with this disorder. Cell-mediated immune status was evaluated in patients with carefully defined CFS and compared with that of matched subjects with major depression (non-melancholic, non-psychotic) as well as healthy control subjects. Patients with CFS demonstrated impaired lymphocyte responses to phytohaemagglutinin (PHA) stimulation, and reduced or absent delayed-type hypersensitivity (DTH) skin responses when compared either with subjects with major depression or with healthy control subjects (P &lt; 0·05 for each analysis). Although depression is common in patients with CFS, the disturbances of cell-mediated immunity in this disorder differ in prevalence and magnitude from those associated with major depression. These observations strengthen the likelihood of a direct relationship between abnormal cell-mediated immunity and the etiology of CFS.
Fcε receptor II/CD23+ lymphocytes in atopic dermatitis. III. Aberrant control in thein vitroexpression of FcεRII/CD23 on peripheral blood T cells in atopic dermatitis
Authors: SAKAMOTO T , NAKAYAMA F , TAMAMORI T , TAKIGAWA M 
Published: July 2010

SUMMARYIn vitro FcεRII expression was examined in patients with atopic dermatitis, those with non-atopic eczematous dermatitis and normal individuals following stimulation of peripheral blood cells with recombinant IL-4 (rIL-4), phytohaemagglutinin (PHA), or PHA plus rIL-2. At various days cells were stained with MoAbs to human lymphocyte FcεRII and to lymphoid cell-surface antigens and analysed by flow cytometry, rIL-4, but not rIL-2, specifically induced FcεRII on T cells as well as B cells in atopic dermatitis, eczematous dermatitis and normal individual groups. Both atopics and non-atopics generated comparable proportions of FcεRII+ T cells (Tε cells), whereas the frequency of B cells bearing FcεRII(Bε cells) was significantly higher in patients with extensive atopic dermatitis than in those with mild atopic dermatitis and other subjects. Comparable levels of Tε cells were detected in both atopic and non-atopic donors following stimulation of peripheral blood cells with PHA or pre-activation of the cells with PHA plus subsequent incubation with rIL-2. Whereas both CD8+ and CD4+ subsets were present in Tε cell populations induced specifically by rIL-4, PHA and PHA plus rIL-2, patients with atopic dermatitis had a greater tendency for FcεRII expression on CD8+ T cells compared with patients with eczematous dermatitis and normal individuals. Recombinant interferon-gamma (rIFN-γ), but not rIFN-α or prostaglandin E2 (PGE2), suppressed the generation of Tε cells by rIL-4 in atopics and non-atopics to the same degree. These results suggest the aberrant control of FcεRII expression on T cells, especially those bearing CD8, in atopic dermatitis.
Prevention of adjuvant arthritis in rats by a nonapeptide from the 65-kD mycobacterial heat shock protein: specificity and mechanism
Authors: YANG X-D , GASSER J , FEIGE U 
Published: July 2010

SUMMARYIn a previous study we have shown that Lewis rats were completely protected from adjuvant arthritis by pretreatment with a nonapeptide (residues 180–188) of the 65-kD mycobacterial heat shock protein. Here we address questions of specificity and mechanism(s) of protection. We demonstrate that complete protection against adjuvant arthritis can only be achieved by pre-immunization with the nonapeptide, while pretreatment with either the octapeptide (residues 181–188) of the 65-kD heat shock protein or unrelated immunogenic peptides failed to affect adjuvant arthritis. Interestingly, pretreatment with the nonapeptide of the 65-kD heat shock protein did not protect Lewis rats from type II collagen-induced arthritis. These results demonstrate that protection is both epitope and disease specific. Co-injection of the nonapeptide with mycobacterial antigen even at a weight ratio of 5:1 (nonapeptide: mycobacteria) failed to influence the disease, suggesting that the role of the nonapeptide is not as a ‘blocking peptide’. T cells from rats immunized with nonapeptide respond to the nonapeptide as well as to mycobactcria in vitro, and adoptively transfer protection to naive recipients. The data indicate that the nonapcptide-induced protection may result from a T cell mediated specific suppression.
Primary structure of a monoclonal κ chain in myeloma with light chain deposition disease
Authors: KHAMLICHI A A , AUCOUTURIER P , SILVAIN C , BAUWENS M , TOUCHARD G , PREUD'HOMME J-L , NAU F , COGNÉ M 
Published: July 2010

SUMMARYPrevious data suggest that structural abnormalities of immunoglobulin light chains may be responsible for non-amyloid light chain deposition disease (LCDD). We report on the complete primary sequence deduced from complementary (c)DNA analysis of a normal-sized κ chain in a case of myeloma-associated LCDD. The patient's urine contained a κ type Bence-Jones protein made of monomers and dimers of an unglycosylated κ chain. The bone marrow myeloma cells contained intracellular κ and γ chains by immunofluorescence. Biosynthesis experiments showed the production of normal-sized γ chains and of κ chains with the same apparent molecular mass (Mr) in SDS gels as the urinary κ chain (26000–27000). These κ chains were secreted as assembled IgG molecules and as a large excess of free monomers and dimers. The complete sequence of two identical cDNA clones derived from a normal-sized κ messenger RNA indicated that this K chain belonged to the rare VκIV subgroup. The κ mRNA had an overall normal structure made up of the VκIV sequence rearranged to JκIV and followed by a normal constant exon of the Km(3) allotype. The variable region differed from the VκIV-JκI germline sequence by 17 amino acid substitutions. The peculiar sequence of the variable region of this κ chain of a rare subgroup might relate lo its tissue deposition.