bluuebunny/crossref_metadata_2025_split huggingface dataset:
The murine immune response to the male‐specific antigen mouse testicular cytochrome c
Authors: Kelner Gregory S. , Minnerath Jeanne M. , Jenkins Marc K. , Jemmerson Ronald 
Published: March 2007

AbstractMale and female A/J mice were examined for their ability to elicit T lymphocyte and antibody (Ab) responses to the male‐specific Ag, mouse testicular cytochrome c (Mt cyt).T lymphocytes from both male and female mice primed in vivo responded to the Ag in in vitro proliferation assays, and the dose‐response curves were statistically indistinguishable. In addition, similar levels of Ab to Mt cyt were observed in immunized male and female mice. The B cells producing the Ab had switched isotypes to IgG1 and IgG2a, indicating that the self‐reactive T helper (Th) cells in male mice were functional. Thus, male mice do not appear to be immunologically tolerant to Mt cyt, at least at the Th and B lymphocyte levels. No evidence for disease was found in male mice primed with Mt cyt. Major histocompatibility complex (MHC) class II‐positive antigen‐presenting cells are present in the testes and these were shown in vitro to process and present Mt cyt to a Tcell hybridoma specific for the synthetic peptide Mt cyt 93‐104. However, the hybridoma was not activated in the absence of exogenous Mt cyt 93‐104 or Mt cyt, indicating that endogenous Mt cyt is not normally processed in sufficient quantity to effectively load MHC class II molecules with this particular Mt cyt‐derived peptide. Notwithstanding any immunologic privilege of the testes, the lack of tolerance to Mt cyt and its failure to elicit an autoimmune disease could extend from the low levels of processed Mt cyt Ag available for T cell recognition. The T cell response elicited by Mt cyt contrasts the lack of response to mouse somatic cytochrome c which differs from Mt cyt at 13 amino acid residues and is expressed in most tissues and at higher levels.
Induction of macrophage nitric oxide production by interferon‐γ and tumor necrosis factor‐α is enhanced by interleukin‐10
Authors: Corradin Sally Betz , Fasel Nicolas , Buchmüller‐Rouiller Yolande , Ransijn Adriana , Smith Josiane , Mauël Jacques 
Published: March 2007

AbstractInterleukin‐10 (IL‐10) has been reported to inhibit nitric oxide (NO) synthesis and microbicidal activity of interferon‐γ (IFN‐γ)‐stimulated macrophages (MΦ) by preventing the secretion of tumor necrosis factor‐α (TNF‐α) which serves as an autocrine activating signal. We have examined the effects of recombinant IL‐10 on the capacity of IFN‐γ together with exogenous TNF‐α to induce NO synthesis by bone marrow‐derived MΦ. Under these conditions and in contrast to its reported deactivating potential, IL‐10 strongly enhanced NO synthesis measured as nitrite (NO) release (half maximal stimulation at approximately 10 U/ml). IL‐10 further increased NO production by MΦ stimulated in the presence of optimal concentrations of prostaglandin E2, a positive modulator of MΦ activation by IFN‐γ/TNF‐α. Increased steady state levels of NO synthase mRNA were observed in 4‐h IFN‐γ/TNF‐α cultures and enhanced NO release was evident 24 h but not 48 h after stimulation. These results suggest that the effects of IL‐10 on MΦ function are more complex than previously recognized.
The Mycobacterium tuberculosis 71‐kDa heat‐shock protein induces proliferation and cytokine secretion by murine gut intraepithelial lymphocytes
Authors: Beagley Kenneth W. , Fujihashi Kohtaro , Black C. Allen , Lagoo Anand S. , Yamamoto Masafumi , McGhee Jerry R. , Kiyono Hiroshi 
Published: March 2007

AbstractMurine intraepithelial lymphocytes (IEL) respond poorly to T cell mitogens and to monoclonal antibody stimulation of T cell receptor (TCR)‐ and CD3‐associated molecules. In contrast, we found that a soluble extract of Mycobacterium tuberculosis (Mtb), but not purified protein derivative of tuberculin, induced significant proliferative responses in IEL cultures. The active component was apparently a heat shock protein (HSP), since recombinant 71‐kDa HSP from Mtb induced IEL to proliferate, while 65‐kDa HSP from M. bovis and M. leprae did not. Both α/β and α/δ TCR‐enriched IEL gave proliferative responses to 71‐kDa HSP. Further, culture supernatants from IEL stimulated with 71‐kDa HSP contained elevated levels of interleukin‐(IL)‐3/granulocyte‐macrophage colony‐stimulating factor, interferon‐y and IL‐6, but not IL‐2, IL‐4, IL‐5 or transforming growth factor‐β Finally, several IEL T cell clones have been maintained for up to 6 weeks, when stimulated with 71‐kDa HSP, IL‐2 and feeder cells. Our results show that the 71‐kDa HSP of Mtb induces IELT cells to divide and to secrete cytokines and this may offer a model for cloning and study of IEL T cells in vitro.
A possible role of two hydrophobic amino acids in antigen recognition by synovial T cells in rheumatoid arthritis
Authors: Maruyama Toshiaki , Saito Ichiro , Miyake Sachiko , Hashimoto Hiroshi , Sato Kazuto , Yagita Hideo , Okumura Ko , Miyasaka Nobuyuki 
Published: March 2007

AbstractSynovial T cells play a crucial role in the pathogenesis of rheumatoid arthritis (RA) synovitis. We have quantitatively analyzed the T cell receptor (TcR) variable (V) region gene repertoire of freshly isolated synovial fluid (SF) T cells, comparing it with that of peripheral blood (PB) T cells in RA. The TcR V gene repertoire of PB and SF T cells in RA and osteoarthritis was heterogeneous. In contrast, Vail in SF was expressed to a greater degree in three of five RA patients, and increased levels of Vp6, 1‐3 were found in the SF of four of six RA, compared with paired PB. Of note, Vβ6, 1–3 was universally used in four RA patients with a disease duration of less than 10 years, irrespective of their HLA‐DR types. This was in contrast to two other RA patients, suffering for more than 20 years, who showed different Vα and Vβ usages. β‐chain sequence analysis in RA patients with a preference for Vβ6, 1–3 has shown that a few clones dominated in SF, whereas polyclonality was observed in PB. These findings suggest oligoclonal expansion of T cells in response to specific antigen(s) in the SF of these patients with RA of relatively short duration. Concomitant use of two hydrophobic amino acids, leucine and valine, in the Dβ region was noticeable among the predominant SF clones. These two amino acids might directly contact a peptide specific for the induction of synovitis in RA patients. TcR‐directed therapy may, therefore, be useful for the treatment of early RA synovitis.
Distribution of perforin‐containing cells in normal and pregnant mice*
Authors: Zheng Li Mou , Ojcius David M. , Young John Ding‐E. 
Published: March 2007

AbstractCytotoxic T lymphocytes (CTL) and natural killer (NK) cells elaborate a cytolytic protein named perforin or cytolysin. It was widely held that, in vivo, high quantities of perforin are not present in resting lymphocytes and are usually produced only by activated lymphocytes found under pathological conditions. Until now, only one tissue was known to synthesize abundant quantities of perforin under nonpathological conditions, the uterus during pregnancy. To investigate the possibility that perforin might also be synthesized by other tissues, several tissues besides the uterus from pregnant and normal mice were tested by immunofluorescence and immunoperoxidase for the presence of perforin. The tissues studied were the ears, brain, nasal epithelium, tongue, salivary gland, larynx, thymus, stomach, liver, spleen, small intestine, and lymph nodes; two cell populations with different sizes and levels of perforin expression were found. Large cells, displaying the NK cell phenotype and expressing high levels of perforin, were detected not only in the uterus but also in the salivary gland and lungs of pregnant mice. Small cells, expressing low levels of perforin, were detected mainly in the stomach and small intestine, and they were expressed in both pregnant and normal mice. Taken together, these results imply that perforin‐containing cells exist in vivo under nonpathological conditions, and that the immune system is endowed with heretofore unknown mechanisms for stimulating the activation of NK cells in a limited number of tissues during pregnancy.
Selective activation of resting human γδ T lymphocytes by interleukin‐2
Authors: Kjeldsen‐Kragh Jens , Quayle Alison J. , Skålhegg BjøRn S. , Sioud Mouldy , Førre Øystein 
Published: March 2007

AbstractIn rheumatoid arthritis and other inflammatory diseases we and others have found that γδ T cells express activation antigens, suggesting that they are involved in the pathogenesis of these disorders. In this study we have stimulated peripheral blood mononuclear cells from normal donors with recombinant interleukin‐2 (rIL‐2) to see whether such a stimulus alone could activate γδ T cells. Short‐term exposure (24‐96 h) to rIL‐2 selectively stimulated the γδ but not the αβ T cells to express activation antigens (CD69, CD25 and HLA‐DR). Long‐term culture (2 weeks) in rIL‐2‐containing medium caused a selective increase in the proportion of the γδ T cells and a corresponding reduction of the fraction of αβ T cells. Limiting dilution analysis revealed that approximately 1/60 of the γδ T cells responded to IL‐2 in contrast to only 1/250 of the αβ T cells. Comparison of the expression of the IL‐2 receptor (IL‐2R) a and P chains showed that there was a similar expression of the α chain on γδ and αβ T cells whereas the relative density of the β chain was more than twice as high on γδ T cells. Both the IL‐2‐induced proliferation of γδ T cells and the expression of activation antigens on these cells could be inhibited by an anti‐IL‐2Rβ monoclonal antibody (mAb) but not by an anti‐IL‐2Rα mAb. Expression of CD69 on γδ T cells was dependent neither on the presence of B cells, monocytes, nor αβ T cells. Finally, we found that the IL‐2‐induced expression of CD69 was inhibited by activation of cAMP‐dependent protein kinase and by inhibition of the Src‐family of the tyrosine protein kinase, but not by inhibition of protein kinase C or by activation of the CD45 associated tyrosine phosphatase. The ability of γδ T cells to be activated by IL‐2 is a feature which they have in common with natural killer cells. Moreover, it may be possible that the expression of activation antigens on γδ T cells in inflammatory diseases is an epiphenomenon secondary to IL‐2 produced by activated αβ T cells.
DR αβ dimers released from complexes with invariant chain fail to stimulate alloreactive T cell clones
Authors: Demotz Stéphane 
Published: March 2007

AbstractTo demonstrate that DR αβ dimers still complexed to invariant chain (Ii) have not yet acquired peptides recognized by alloreactive T cells, complexes between DR molecules and Ii isolated from Epstein‐Barr‐virus (EBV)‐transformed B cells were analyzed by affinity chromatography and gel filtration. First, it was shown that DR/Ii complexes inserted into artificial planar membranes (PM) failed to stimulate proliferative response of five alloreactive T cell clones and a polyclonal alloreactive Tcell line, while PM bearing mature DR αβ dimers from the same EBV‐B cells were stimulatory for the Tcell clones and the Tcell line. These findings indicate that either Ii inhibits binding of peptides to DR molecules or Ii hinders T cells recognition of peptide/DR complexes. Second, to discriminate between these two possibilities, DR αβ dimers, which were artificially released from complexes between DR molecules and Ii, were inserted into PM. These DR αβ dimers were devoid of alloreactive stimulatory capacity while fully capable of binding and presenting a tetanus toxin synthetic peptide to a specific Tcell clone, indicating that DR molecules released from complexes with Ii are empty. This study, by showing that DR molecules bound to Ii do not bear peptides recognized by alloreactive T cells, supports the notion that association of Ii with class II major histocompatibility complex (MHC) molecules prevents premature peptide loading and hence favors encounter with peptides derived from proteins of the extracellular compartment.Since allogeneic class II MHC molecules released from complexes with Ii were not stimulatory for five out of five alloreactive Tcell clones and a polyclonal alloreactive Tcell line, these data also indicate that, in most cases, alloreactive T cells recognize ligands constituted by complexes between allogeneic class II MHC molecules and specific peptides which derive from the antigen‐presenting cells themselves or serum proteins.
Activator protein‐1 (AP‐1) is stimulated by microbial superantigens in human monocytic cells
Authors: Trede Nikolaus S. , Chatila Talal , Geha Raif S. 
Published: March 2007

AbstractMicrobial superantigens bind to major histocompatibility complex (MHC) class II molecules and activate gene transcription in monocytes. In search of transcription factors that potentially mediate the effects of superantigens at the nuclear level, we examined the capacity of staphylococcal superantigens to stimulate the activity of the transcriptional promoter factor activator protein‐1 (AP‐1). Electrophoretic mobility shift assays showed an increase in nuclear proteins that bound to the consensus AP‐1 motif within 5 min following the stimulation of the monocytic cell line THP‐1 with toxic shock syndrome toxin‐1 (TSST‐1) or staphylococcal entotoxin A. We show that mRNA levels for the subunits that compose AP‐1, the protooncogenes c‐fos and c‐jun, are up‐regulated by stimulation of THP‐1 cells with TSST‐1. The activated AP‐1 complexes were functional, as evidenced by the capacity of TSST‐1 to stimulate the expression of an AP‐1‐driven reporter gene construct transfected into THP‐1 cells. These results establish that the engagement of MHC class II molecules by superantigens increases the activity of functional AP‐1 complexes and that this may proceed in part by transcriptional activation of c‐fos and c‐jun protooncogenes.
The interleukin‐12 subunit p40 specifically inhibits effects of the interleukin‐12 heterodimer
Authors: Mattner Frank , Fischer Susanne , Guckes Stefanie , Jin Shenchu , Kaulen Hildegard , Schmitt Edgar , Rüde Erwin , Germann Tieno 
Published: March 2007

AbstractThe recently discovered cytokine interleukin (IL)‐12 is a heterodimeric protein of two disulfide‐bonded subunits of 35 and 40 kDa. IL‐12 has multiple effects on T cells and natural killer (NK) cells. In particular it appears to be a major factor for the development of cellular immunity. So far activity of the single subunits alone has not been described, however their expression is regulated independently. In this report we demonstrate for the first time that the mouse IL‐12 subunit p40 (IL‐12p40) specifically antagonizes the effects of the IL‐12 heterodimer in different assay systems. The proliferation of mouse splenocytes activated by phorbol ester and IL‐12 was inhibited by IL‐12p40, whereas the proliferation induced by phorbol ester and IL‐2 was not affected. Furthermore, the synthesis of interferon (IFN)‐γ by mouse splenocytes activated with IL‐2 and IL‐12 was suppressed by IL‐12p40. Purified mouse splenic CD4+ T cells produced IFN‐γ upon activation with plate‐bound anti‐CD3 monoclonal antibody which was enhanced more than tenfold in the presence of IL‐12. In this system IL‐12p40 inhibited only the enhancement caused by IL‐12 but not IFN‐γ synthesis of CD4+ T cells stimulated with anti‐CD3 alone. Moreover, IL‐12p40 inhibited the effects of IL‐12 on differentiated T helper type 1 (Th1) cells. IFN‐γ production by Th1 cells induced in a T cell receptor‐independent way by macrophages and IL‐2 or macrophages and IL‐12 was greatly reduced by IL‐12p40 providing evidence for the endogenous synthesis of IL‐12 in the Th1 cell, macrophage and IL‐2 co‐cultures. The specificity of inhibition was clearly demonstrated in the homotypic aggregation assay of Th1 cells. Incubation of Th1 cells with either IL‐2 and IL‐12 or IL‐2 and tumor necrosis factor induces LFA‐1/ICAM‐1‐dependent aggregation. Only IL‐2 + IL‐12 but not IL‐2 + tumor necrosis factor‐induced aggregation was inhibited in a dose‐dependent manner by IL‐12p40. Thus, the IL‐12 subunit p40 appears to be a specific inhibitor for the IL‐12 heterodimer.
Modification of the anti‐CD3‐induced cytokine release syndrome by anti‐interferon‐γ or anti‐interleukin‐6 antibody treatment: Protective effects and biphasic changes in blood cytokine levels
Authors: Matthys Patrick , Dillen Chris , Proost Paul , Heremans Hubertine , And Jo Van Damme , Billiau Alfons 
Published: March 2007

AbstractAnti‐interferon‐γ (IFN‐γ) antibodies were found to protect mice against pathological changes induced by injection of anti‐CD3 antibody: incidence of diarrhea, severity of hypothermia and mortality rates were dramatically reduced. In anti‐IFN‐γ antibody‐treated mice, IFN‐γ blood levels were significantly reduced at 1.5 h post anti‐CD3 challenge, but more elevated levels were found from 4 to 24 h. This rebound‐like IFN‐γ response coincided with more profound hypoglycemia. Tumor necrosis factor and interleukin (IL)‐6 levels were not affected by anti‐IFN‐γ treatment. Exogenous IFN‐γ, administered within 3 h (but not later) of the anti‐CD3 challenge made the syndrome worse. Furthermore, inter‐mouse strain differences in sensitivity to the anti‐CD3 syndrome correlated with the ability of the strain to produce IFN‐γ. Anti‐IL‐6 antibodies provided only marginal protection against hypothermia and mortality, but did markedly reduce hypoglycemia. Levels of biologically active IL‐6 in serum were not influenced by anti‐IL‐6 antibody treatment during the first few hours after anti‐CD3 challenge, but were significantly increased at later times.The data provide evidence that endogenous IFN‐γ is a critical element in the early phase of the anti‐CD3 syndrome; endogenous IL‐6, while possibly being involved in hypoglycemia, seems of lesser importance for the outcome of the syndrome.
Growth requirements for avian γδ T cells include exogenous cytokines, receptor ligation and in vivo priming
Authors: Kasahara Yoshihito , Chen Chen‐Lo H. , Cooper Max D. 
Published: March 2007

AbstractThese studies analyze growth requirements for the normal γδ T cell population in peripheral lymphoid tissues. Avian γδ T cells can respond well to T cell mitogens in the presence of αβ T cells, but our studies indicate that they do not grow well alone. Exogenous growth factors were required in order for γδ T cells to proliferate in response to receptor ligation by anti‐T cell receptor antibodies or other T cell mitogens. Interleukin‐2 was implicated as one of the necessary growth factors that the γδ cells cannot produce adequately on their own. The response to dual stimulation (receptor ligation plus exogenous T cell factors) was attributable to a discrete subpopulation of γδ T cells that could be identified by their cell surface CD8, major histocompatibility complex class II expression and relative increase in cell size. Conversely, non‐responsive γδ T cells did not exhibit these activation markers. These observations suggest a physiological basis for the relatively late appearance of γδ T cells in inflammatory responses and their failure as a population to match the growth potential of αβ T cells. More importantly, the results imply that the biological role of γδ T cells must be understood within the context of their interaction with αβ T cells.
Role of transforming growth factor‐βthe preferential induction of T helper cells of type 1 by staphylococcal enterotoxin B
Authors: Nageikerken Lex , Gollob Kenneth J. , Tielemans Margret , Coffman Robert L. 
Published: March 2007

AbstractStimulation of murine CD4+ T cells with staphylococcal enterotoxin B (SEB) results in the preferential development of T helper (Th) 1 cells [i.e. high interferon (IFN)‐γ and low interleukin (IL)‐4, IL‐5 and IL‐10]; whereas in response to plate‐bound anti‐CD3 or anti‐T cell receptor‐αβ, Th1 as well as Th2 cells develop. In the present study, we examined the mechanism which is responsible for the selective Th1 development in the SEB system. The addition of IL‐4 resulted in a strong development of Th2 cells showing that SEB stimulation can result inTh2 differentiation. Co‐stimulation with anti‐CD28 was insufficient in this regard. Lack of Th2 development in the SEB system was in part due to the inhibitory effect of endogenously produced transforming growth factor‐β (TGF‐β), because anti‐TGF‐β allowed the development of Th2 cells. Similarly, TGF‐β inhibited Th2 development and stimulated Th1 development in the anti‐CD3 system. This shift was only partially prevented by also including IL‐4 in the cultures. The effects of TGF‐β could only partially be explained by stimulation of IFN‐γ or inhibition of IL‐4 as intermediatory cytokines: (1) TGF‐β stimulated Th1 development even in the presence of anti‐IL‐4 and anti‐IFN‐γ, and (2) a strong inhibitory effect of anti‐TGF‐β on Th1 development was still observed when anti‐IL‐4 and IFN‐γ were simultaneously added to the cultures. It is concluded that SEB favors Th1 development by stimulation of TGF‐β production. Inhibition of Th2 development by TGF‐β is due, in part, to inhibition of IL‐4 and stimulation of IFN‐γ, and, in part, to a direct effect of TGF‐β on the responding T cells.
CD40 ligand is a T cell growth factor
Authors: Armitage Richard J. , Tough Teresa W. , Macduff Brian M. , Fanslow William C. , Spriggs Melanie K. , Ramsdell Fred , Alderson Mark R. 
Published: March 2007

AbstractCD40 ligand (CD40L) is a 33‐kDa type II membrane glycoprotein induced on T cells upon activation. CD40L has previously been shown to induce proliferation of resting B cells, immunoglobulin (Ig) secretion from B cells cultured with cytokines and cytokine secretion and tumoricidal activity from monocytes. In this report CD40L is shown to be stimulatory for human T cells, inducing CD25 (p55 IL‐2R) and CD40L expression on resting peripheral blood T cells, enhanced expression of these molecules and CD69 on CD3‐activated cells and secretion of interferon‐y, tumor necrosis factor‐a and interleukin (IL)‐2 from T cells cultured in the presence of a sub‐mitogenic concentration of phytohemagglutinin A (PHA). Furthermore, stimulation with CD40L induces proliferation of CD3‐ or PHA‐activated T cells of blood, tonsillar or thymic origin. A similar proliferative response is observed with CD4− and CD8+ T cells and this effect is largely IL‐2 independent. A soluble construct of the extracellular domain of the CD40L has similar activity to that of membrane‐expressed ligand in the induction of T cell surface antigens and proliferation. The results presented here taken together with the various activities ascribed for CD40L on B cells and monocytes demonstrate that CD40L has pleiotropic biological activity for cells of the hemopoietic lineage.