bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pregnancies modulate B lymphopoiesis and myelopoiesis during murine ageing
Authors: Barrat F. S. , Lesourd B. M. , Louise A. S. , Boulouis H.‐J. , Thibault D. J. , Neway T. , Pilet C. A. 
Published: March 2003

SummaryWe recently reported that pregnancy affects age‐related changes in the distribution of lymphoid and macrophage populations in the spleen of C57Bl/6 mice. In the present study, we examined the influence of pregnancies on the generation of various developmental B‐cell subsets and granulocyte/macrophage lineage cells during murine ageing. Using flow cytometry, changes in lymphoid (mature and early B‐cell precursors: B220high, B220low, surface immunoglobulin M (sIgM) µ chain +/−) and myeloid (monocyte/macrophage Mac‐1/CD11b, granulocyte Gr‐1/Ly‐6G) compartments were monitored in the bone marrow of young (2 months) and 15‐ and 23‐month‐old mice including male, multiparous and virgin female mice. Pregnancies delayed the age‐related decline in murine B lymphopoiesis and maintained B‐cell reserve capacity during ageing. We also found an increased production of myeloid cells induced by pregnancies at middle (15 months) and advanced (23 months) ages. This comparative study provides new information on changes in marrow lymphopoiesis and myelopoiesis with age. Our data emphasizes that the onset, magnitude and kinetics of age‐related changes in the haematopoietic marrow are parity dependent. These changes could influence the incidence of age‐related diseases and may account for the greater longevity of females.
Contrasting effects of myeloid dendritic cells transduced with an adenoviral vector encoding interleukin‐10 on organ allograft and tumour rejection
Authors: Lee, W.‐C. , Qiani, S. , Wan Y. , Li, W. , Xing, Z. , Gauldie, J. , Fung, J. J. , Thomson A. W. , Lu L. 
Published: March 2003

SummaryMouse bone marrow‐derived myeloid dendritic cells (DC) propagated in granulocyte–macrophage colony‐stimulating factor and transforming growth factor‐β1 (TGF‐β1) (so‐called ‘TGF‐β DC’) are phenotypically immature, and prolong allograft survival. Interleukin‐10 (IL‐10) has been shown to inhibit the maturation of DC by down‐regulating surface major histocompatibility complex (MHC) class II, co‐stimulatory and adhesion molecule expression. Genetic engineering of TGF‐β DC to overexpress IL‐10 might enhance their tolerogenic potential. In this study, adenoviral (Ad) vectors encoding the mouse IL‐10 gene were transduced into B10 (H2b) TGF‐β DC. Transduction with Ad‐IL‐10 at a multiplicity of infection (MOI) of 50–100 resulted in a modest reduction in the incidence of DC expressing surface MHC class II, CD40, CD80 and CD86. Paradoxically, Ad‐IL‐10 transduction enhanced the allostimulatory activity of DC in mixed leucocyte reactions and cytotoxic T lymphocyte assays, and increased their natural killer cell stimulatory activity. Systemic injection of normal C3H recipients with Ad‐IL‐10‐transduced B10‐DC 7 days before organ transplantation, exacerbated heart graft rejection and augmented circulating anti‐donor alloantibody titres. Contrasting effects were observed in relation to tumour growth. All mice preimmunized with Ad‐IL‐10‐transduced, tumour antigen (B16F10)‐pulsed DC developed palpable tumours, associated with significant inhibition of splenic anti‐tumour cytotoxic T lymphocyte generation. Animals pretreated with control Ad‐LacZ‐transduced, B16F10‐pulsed DC however, remained tumour free. These findings are consistent with the multifunctional immunomodulatory properties of mammalian IL‐10.
The lipid A region of lipopolysaccharides from Rhizobiaceae activates bone marrow granulocytes from lipopolysaccharide‐hyporesponsive C3H/HeJ andC57BL/10ScCr mice
Authors: Pedron T. , Girard R. , Jeyaretnam B. , Carlson R. W. , Chaby R. 
Published: March 2003

SummaryWe established in previous studies that the binding of Salmonella lipopolysaccharide (LPS) to constitutive receptors of low affinity triggers the expression of the inducible LPS‐binding molecule CD14 in bone marrow cells (BMC) of C3H/HeOU mice, but not in BMC from C3H/HeJ mice. We show in this study that BMC from C3H/HeJ and C57BL/10ScCr mice do not express CD14 after exposure to LPSs from Salmonella enterica and Bordetella pertussis, but do express this marker when treated with several LPSs from Rhizobiaceae, or their lipid A fragments. This shows that the constitutive LPS receptor in BMC from C3H/HeJ and C57BL/10ScCr mice is fully able to trigger a complete signalling cascade. Results of cross‐inhibition of the binding of radiolabelled LPS indicated that active LPSs (from R. species Sin‐1 and R. galegae) and inactive LPSs (from S. enterica and B. pertussis) bind to the same site of the constitutive LPS receptor of C3H/HeJ cells. Furthermore, binding of R. species Sin‐1 LPS, and signalling induced by this LPS, were both inhibited by pre‐exposure of C3H/HeJ cells to B. pertussis lipid A. This correlation between binding and signalling suggests that in C3H/HeJ cells, the constitutive receptor, which recognizes a large panel of LPSs from different origins, appears selectively unable to be activated by some particular LPSs, such as those of Enterobacteria and Bordetella.
Distribution of, and immune response to, chicken anti‐αGal immunoglobulin Y antibodies in wild‐type and αGal knockout mice
Authors: Walsh Jr W. E. , Anderson B. E. , Ivancic D. , Zhang Z. , Piccini J. P. , Rodgers T. G. , Pao W. , Fryer J. P. 
Published: March 2003

SummaryChicken antibodies (immunoglobulin Y; IgY) to the αGal epitope (galactose α‐1,3‐galactose) bind to αGal antigens of mouse and porcine tissues and endothelial cells in vitro and block human anti‐αGal antibody binding, complement activation and antibody‐dependent cell‐mediated lysis mechanisms. The activities and toxicity of anti‐αGal IgY have not been tested in vivo. In this study, we tested the effects of multiple injections of affinity‐purified anti‐αGal IgY (AP‐IgY) in both wild‐type (WT) and α‐1,3‐galactosyltransferase knockout (Gal KO) mice. WT and Gal KO mice were injected once, twice, three, or four times intravenously (i.v.) with AP‐IgY and killed at 1 hr or 24 hr. Mice displayed no toxicity to four injections of AP‐IgY. Heart, lung, liver, kidney, spleen and pancreatic tissue were evaluated using immunohistochemical techniques for the presence of the αGal epitope using the GSI‐B4 lectin, and for bound IgY, as well as mouse IgM and IgG. The binding of AP‐IgY antibodies to the endothelium of WT mouse tissues was essentially identical to the pattern of binding of the GSI‐B4 lectin after injection of WT mice and death at 1 hr. WT mice killed 24 hr after i.v. injection of AP‐IgY showed little remaining bound IgY in their endothelia, indicating that IgY is cleared over that time period. We also evaluated the blood drawn at the time of death for the presence of anti‐αGal IgY, anti‐IgY IgM and anti‐IgY IgG by enzyme‐linked immunosorbent assay. Anti‐αGal IgY was almost undetectable in WT mouse sera at all injection and killing times. In contrast, Gal KO mouse sera showed increasing anti‐αGal IgY levels until 24 hr after the fourth injection, when anti‐αGal IgY levels were almost undetectable. Anti‐IgY IgM and IgG levels in WT and Gal KO mouse sera showed a typical increase in anti‐IgY IgM 24 hr after the second injection (3 days after the first injection) and an increase in anti‐IgY IgG 24 hr after the third injection (5 days after the first injection). These results show that IgY binds to αGal epitopes in the WT mice and is cleared sometime over a 24‐hr time period and that IgY is an expected immunogen in mice eliciting a rather typical anti‐IgY IgM and IgG response.
Inhibition of contact sensitivity in human CD4+ transgenic mice by human CD4‐specific monoclonal antibodies: CD4+ T‐cell depletion is not required
Authors: Podolin P. L. , Webb E. F. , Reddy M. , Truneh A. , Griswold D. E. 
Published: March 2003

SummaryClenoliximab and keliximab are monkey/human chimeric monoclonal antibodies (mAbs) of the immunoglobulin G4 (IgG4) and IgG1 isotypes, respectively, that recognize the same epitope on human CD4. The two mAbs possess identical idiotypes and exhibit equal affinities for CD4. Upon administration of these mAbs to mice that express a human CD4 transgene, but not mouse CD4 (HuCD4/Tg mice), clenoliximab and keliximab exhibited similar kinetics of binding to CD4, and induced the same degree of CD4 modulation from the cell surface, although only keliximab mediated CD4+ T‐cell depletion. Epicutaneous sensitization and challenge of HuCD4/Tg mice with the hapten oxazolone resulted in a contact sensitivity response characterized by tissue swelling, and the presence of interferon‐γ (IFN‐γ) and interleukin‐4 (IL‐4) in the local tissue. Administration of a single 2‐mg dose of either clenoliximab or keliximab to HuCD4/Tg mice prior to sensitization significantly reduced post‐challenge tissue swelling, and levels of IFN‐γ and IL‐4, indicating that CD4+ T‐cell depletion is not required for anti‐CD4 mAb‐mediated inhibition of contact sensitivity. Administration of either mAb prior to challenge failed to inhibit the contact sensitivity response, indicating differential sensitivity of the afferent and efferent phases of the response to inhibition by CD4‐specific mAbs. Collectively, these data indicate that CD4 functions as a positive regulatory molecule in the contact sensitivity response.
CD40–CD40 ligand (CD154) engagement is required but may not be sufficient for human T helper 1 cell induction of interleukin‐2‐ or interleukin‐15‐driven, contact‐dependent, interleukin‐1β production by monocytes
Authors: Ribbens C. , Dayer J.‐M. , Chizzolini C. 
Published: March 2003

SummaryTo investigate whether antigen‐independent, interleukin‐2 (IL‐2) or IL‐15 activation of polarized T helper (Th) cells would result in contact‐dependent activation of monocytes, living Th1 and Th2 cell clones were co‐cultured with THP‐1 cells or fresh peripheral blood monocytes. Under these conditions IL‐1β production was induced almost exclusively by Th1 cells and was dependent on the presence and dose of IL‐2 or IL‐15, and on cell–cell contact, as demonstrated by double‐chamber cultures. Low levels of IL‐1 receptor antagonist (IL‐1Ra) were induced by Th1 and higher levels by Th2 cells. IL‐10 production was similar in Th1/monocyte and Th2/monocyte co‐cultures, thus arguing against preferential down‐regulation of IL‐1β production by anti‐inflammatory IL‐10 in Th2 co‐cultures. In addition, IL‐4 and IL‐10 neutralization did not result in enhanced IL‐1β production in Th2/monocyte co‐cultures. Preferential expression on Th1 cells of CD11b correlated with their capacity to induce IL‐1β production by THP‐1 cells in the presence of IL‐2 or IL‐15, but anti‐CD11b monoclonal antibody could not inhibit this activity. Blockade of the CD40–CD40 ligand interaction resulted in inhibition of IL‐1β‐inducing capacity while IL‐1Ra induction was unaffected, a result previously unknown. This differential effect indicates the selective relevance of CD40–CD40 ligand engagement in inflammatory monocyte responses upon activation by T cells. CD40 ligand expression levels did not differ in Th1 and Th2 cell clones, thus indicating that additional, unidentified molecule(s) preferentially expressed by Th1 cells are involved in their IL‐1β induction capacity.
A novel CD18 genomic deletion in a patient with severe leucocyte adhesion deficiency: a possible CD2/lymphocyte function‐associated antigen‐1 functional association in humans
Authors: Allende L. M. , Hernández M. , Corell A. , García‐pérez M. A. , Varela P. , Moreno A. , Caragol I. , García‐martín F. , Guillén‐perales J. , Olivé T. , Español T. , Arnaiz‐villena A. 
Published: March 2003

SummaryLeucocyte adhesion deficiency (LAD) is an autosomal‐recessive genetic disease that is characterized clinically by severe bacterial infections and caused by mutations in the CD18 gene that codes for the β2 integrin subunit. A patient with a severe LAD phenotype was studied and the molecular basis of the disease was identified as a single homozygous defect in a Herpes virus saimiri (HVS)‐transformed T‐cell line. The defect identified involves a deletion of 171 bp in the cDNA that encodes part of the proteic extracellular domain. This genetic abnormality was further studied at the genomic DNA level and found to consist of a deletion of 169 bp (from − 37 of intron 4 to + 132 of exon 5), which abolishes the normal splicing and results in the total skipping of exon 5. The 171‐bp shortened ‘in‐frame’ mRNA not only resulted in the absence of CD18 expression on the cell surface but also in its absence in the cytoplasm of HVS T‐cell lines. Functionally, the LAD‐derived HVS T‐cell lines showed a severe, selective T‐cell activation impairment in the CD2 (but not in the CD3) pathway. This defect was not reversible when exogenous interleukin‐2 (IL‐2) was added, suggesting that there is also a functional interaction of the lymphocyte function‐associated antigen‐1 (LFA‐1) protein in the CD2 signal transduction pathway in human T cells, as has been previously reported in mice and in the human Papillon–Lefèvre syndrome. Thus, HVS transformation is not only a suitable model for T‐cell immunodeficiency studies and characterization, but is also a good system for investigating the immune system in pathological conditions. It may also be used in the future in cellular models for in vitro gene‐therapy trials.
Interleukin‐16 stimulates the expression and production of pro‐inflammatory cytokines by human monocytes
Authors: Mathy N. L. , Scheuer W. , Lanzendörfer M. , Honold K. , Ambrosius D. , Norley S. , Kurth R. 
Published: March 2003

SummaryInterleukin‐16 (IL‐16) acts as a chemoattractant for CD4+ cells, as a modulator of T‐cell activation, and plays a key role in asthma. This report describes the cytokine‐inducing effects of IL‐16 on total peripheral blood mononuclear cells (PBMC) and PBMC subpopulations. While CD4+ T lymphocytes did not secrete cytokines in response to rhIL‐16, CD14+ CD4+ monocytes and maturing macrophages secrete IL‐1β, IL‐6, IL‐15 and tumour necrosis factor‐α (TNF‐α) upon rhIL‐16 stimulation. The mRNA species for these four cytokines were detected as early as 4 hr post‐stimulation, with protein being secreted by 24 hr. Secretion of IL‐1β and IL‐6 by total PBMC was dose dependent, with maximal secretion being observed using 50 ng/ml rhIL‐16. However, for IL‐15 or TNF‐α maximal secretion by total PBMC occurred with all concentrations between 5 ng/ml to 500 ng/ml rhIL‐16. Purified monocytes/macrophages secreted maximal concentrations of all four cytokines in the presence of 500 ng/ml rhIL‐16, except for monocytes where maximal secretion of IL‐15 was, interestingly, observed with only 50 ng/ml rhIL‐16. The use of higher concentrations of rhIL‐16 (1000 ng/ml) inhibited secretion of all four cytokines. While these IL‐16‐induced cytokines are likely to be involved in the immune system's response to antigen, the data suggest that IL‐16 may play a key role in initiating and/or sustaining an inflammatory response.
Most parasite‐specific CD8+ cells in Trypanosoma cruzi‐infected chronic mice are down‐regulated for T‐cell receptor‐αβ and CD8 molecules
Authors: Grisotto M. G. , D'Império Lima M. R. , Marinho C. R. F. , Tadokoro C. E. , Abrahamsohn I. A. , Alvarez J. M. 
Published: March 2003

SummaryThe present study shows that CD8+ T lymphocytes expressing low levels of T‐cell receptor (TCR)αβ, CD8 and CD3 accumulate in the spleen, blood, peritoneum and liver, but not in the lymph nodes of mice chronically infected with Trypanosoma cruzi. Analysis of spleen lymphocytes reveals that most CD8LOW TCRLOW T cells have an experienced phenotype (CD44HIGH CD62LLOW and CD45RA,B,CLOW). These cells have small size, lack activation markers such as CD69, CD25 and CD11b (Mac‐1), and do not spontaneously secrete cytokines, suggesting they are at the resting state. When stimulated in vitro with T. cruzi‐infected macrophages, TCRLOW CD8LOW T cells behave as parasite‐specific memory cells, readily responding with interferon‐γ (IFN‐γ) production. Indeed, among parasite‐activated CD8+ lymphocytes, IFN‐γ production was mostly due to TCRLOW CD8LOW cells. Upon in vitro stimulation with anti‐CD3/CD28 monoclonal antibodies, down‐regulated cells produce IFN‐γ and tumour necrosis factor‐α, but not interleukin IL‐10 or IL‐4. Our results indicate that despite parasite persistence, most T. cruzi‐specific experienced CD8+ cells are resting. Nevertheless, when encountering infected macrophages these cells differentiate to Tc1 effectors.
The ability of heat‐killed Mycobacterium vaccae to stimulate a cytotoxic T‐cell response to an unrelated protein is associated with a 65 kilodalton heat‐shock protein
Authors: Skinner M. A. , Prestidge R. , Yuan S. , Strabala T. J. , Tan P. L. J. 
Published: March 2003

SummaryExogenous antigens are generally presented by Class II major histocompatibility (MHC) molecules. When administered with an adjuvant, however, they are capable of inducing a CD8+ T‐cell response where antigen recognition is associated with Class I MHC. Accordingly, immunization with soluble ovalbumin (OVA) alone does not activate CD8+ cytotoxic T cells (CTL) but when given in complete Freund's adjuvant (CFA), or in formulations of a number of novel adjuvants, an OVA‐specific CD8+ CTL response can be detected. We show in this report that immunization with soluble OVA mixed with heat‐killed Mycobacterium vaccae, but not with other common pathogenic and saprophytic mycobacteria, can activate OVA‐specific CD8+ CTL. An OVA‐specific CTL response is detected when mice are immunized by either the intraperitoneal or intranasal route and their spleen cells are re‐stimulated in vitro. Adjuvant activity of heat‐killed M. vaccae is present in M. vaccae culture filtrate, in soluble protein components of whole M. vaccae and in the 65 kDa heat‐shock protein (hsp) of M. vaccae. Mycobacterium vaccae has previously been shown to have no adverse side‐effects in humans. The current results suggest that M. vaccae may be useful as an adjuvant for vaccines and other immunotherapies where CD8+ CTL responses to exogenous proteins are crucial.
Early Vλ diversification in sheep
Authors: Jeong Youngkee , Osborne Barbara A. , Goldsby Richard A. 
Published: March 2003

SummaryThis study examined a number of tissues during early gestation in foetal sheep to determine the earliest site of Vλ expression and time of generation of the Vλ repertoire. Tissues, including spleen, liver, gut, blood and bone marrow, were obtained from 48, 55, 60 and 63 gestational day (g.d.) ovine foetuses and cDNA libraries were prepared from them by reverse transcription–polymerase chain reaction. Clones were randomly selected from cDNA libraries and subjected to sequencing. Analysis of these sequences and comparison with a pool of germline genes led to the following conclusions. The expression of Vλ occurs earlier in spleen (48 g.d.) than in all of the other tissues examined. Also, diversity is seen earlier and at higher levels in early foetal spleen than in all of the other tissues examined. In this regard, it is notable that splenic Vλ expression is readily apparent even before such gut‐associated lymphoid tissue as the ileal Peyer's patch (IPP) has developed. Two germline Vλ genes, 5.1 and 5.3 predominate in early immunoglobulin λ light‐chain gene rearrangement. Examination of Jλ usage revealed the existence of a new Jλ gene and its utilization during the early phases of the development of the ovine antibody repertoire. This study indicates that sites other than the IPP contribute to the diversification of the Vλ repertoire in sheep. We suggest that it is likely that foetal spleen may provide a partially diversified B‐cell repertoire before the IPP becomes active as a major site for massive clonal expansion and extensive diversification of B cells.
Upregulation of CD4 on CD8+ T cells: CD4dimCD8bright T cells constitute an activated phenotype of CD8+ T cells
Authors: Sullivan Yvonne B. , Landay Alan L. , Zack Jerome A. , Kitchen Scott G. , Al‐Harthi Lena 
Published: March 2003

SummaryAside from an intermediate stage in thymic T‐cell development, the expression of CD4 and CD8 is generally thought to be mutually exclusive, associated with helper or cytotoxic T‐cell functions, respectively. Stimulation of CD8+ T cells, however, induces the de novo expression of CD4. We demonstrate that while superantigen (staphylococcal enterotoxin B, SEB) and anti‐CD3/CD28 costimulation of purified CD8+ T cells induced the expression of CD4 on CD8+ T cells by 30 and 17%, respectively, phytohaemagglutinin (PHA) stimulation did not induce CD4 expression on purified CD8+ T cells but significantly induced the expression of both CD4 on CD8 (CD4dimCD8bright) and CD8 on CD4 (CD4brightCD8dim) T cells in unfractionated peripheral blood mononuclear cells (PBMC). The level of the PHA‐mediated induction of CD4dimCD8bright and CD4brightCD8dim was at 27 and 17%, respectively. Depletion of CD4+ T cells from PBMC abrogated this PHA‐mediated effect. Autologous CD4+ and CD8+ T‐cell co‐cultures in the presence of PHA induced this CD4dimCD8bright T‐cell expression by 33%, demonstrating a role for CD4 cells in the PHA‐mediated induction of the double positive cells. The induction of CD4dimCD8bright was independent of a soluble factor(s). Phenotypic analysis of CD4dimCD8bright T cells indicated significantly higher levels of CD95, CD25, CD38, CD69, CD28, and CD45RO expression than their CD8+CD4− counterparts. CD4dimCD8bright T cells were also negative for CD1a expression and were predominately T‐cell receptor (TCR) αβ cells. Our data demonstrate that CD4dimCD8bright T cells are an activated phenotype of CD8+ T cells and suggest that CD4 upregulation on CD8+ T cells may function as an additional marker to identify activated CD8+ T cells.
Fcγ receptor polymorphisms in populations in Ethiopia and Norway
Authors: Van Den Berg Linda , Myhr Kjell‐Morten , Kluge Beate , Vedeler Christian A. 
Published: March 2003

SummarySeventy‐seven healthy Ethiopians were genotyped for polymorphisms in the immunoglobulin G Fc receptors (FcγR) FcγRIIa, FcγRIIIa and FcγRIIIb, including the SH allele. The genotype and allele frequencies were compared with those of 96 healthy Norwegians. Ethiopians had higher frequencies of the SH‐FcγRIIIb (P = 0·001), FcγRIIIa‐158 V (P = 0·026) and FcγRIIIb‐Na2 (P = 0·046) alleles. The genotype distributions of FcγRIIa, FcγRIIIa and FcγRIIIb, however, did not differ significantly from those of the Norwegians. The data were also compared with those reported from studies on other ethnic groups. The variation of different polymorphisms both within and between ethnic groups may influence differences in the incidence rates of infectious and autoimmune diseases.