bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human CD8+ intraepithelial T lymphocytes are mainly CD45RA−RB+ and show increased co‐expression of CD45R0 in celiac disease
Authors: Halstensen Trond S. , Scott Helge , Brandtzaeg Per 
Published: March 2007

AbstractExpression of various CD45 isoforms (RA, RB and R0) on CD3+, CD4+ and CD8+ intraepithelial and lamina propria T cells was examined in situ by a three‐color immunofluorescence technique in jejunal biopsy specimens from 32 patients with celiac disease and 18 controls. The median percentage of CD3+ intraepithelial lymphocytes (IEL) that expressed CD45R0 increased from 52% in controls to 69% in untreated celiac disease (p < 0.01). Furthermore, the percentages of CD4+ and CD8+ IEL strongly positive for CD45R0 rose respectively from 94% and 24% in controls to 100% and 55% in untreated celiac disease. Conversely, CD45R0 was strongy expressed on most CD3+ lamina propria lymphocytes (LPL) both in control (81%) and diseased (77%–81%) mucosa. A variable fraction of the intraepithelial and lamina propria CD3+ T cells expressed mainly CD45RB (controls, 46% and 20%, respectively; celiac disease, 29% and 15%). Only 2% IEL and 4% LPL were positive for CD45RA. Expression of different CD45R isoforms thus identified three distinct CD8+ T cell subsets in human intestinal mucosa. In addition, our results suggested that antigen‐primed CD8+CD45R0+ memory cells accumulate in the jejunal epithelium of patients with untreated celiac disease.
Activation of human B lymphocytes by nanogram concentrations of anti‐IgM‐dextran conjugates
Authors: Rehe Gregory T. , Katona Ildy M. , Brunswick Mark , Wahl Larry M. , June Carl H. , Mond James J. 
Published: March 2007

AbstractSurface immunoglobulin (sIg) cross‐linking on B lymphocytes by high concentrations of anti‐Ig antibody has been used to mimic antigen‐stimulated B cell activation. In order to develop a system to study sIg‐mediated Tcell‐independent B cell activation using low concentrations of anti‐Ig antibody that more closely resemble the concentrations of antigen that are achieved under in vivo conditions, we conjugated monoclonal anti‐human IgM antibody (anti‐μ) to dextran (molecular weight 2 × 106) thereby increasing its valency. This dextran conjugate (anti‐μ‐Dex) stimulated comparable levels of thymidine incorporation and B cell size increases as were seen with unconjugated anti‐μ but at 100‐ to 1000‐fold lower concentrations. Anti‐μ‐Dex also stimulated increases in intracellular ionized calcium ([Ca2+]i) in a higher percentage of cells, of greater magnitude and of longer duration than that stimulated by unconjugated anti‐μ. Interestingly, there was no direct correlation between the increases in [Ca2+]i that were stimulated by anti‐μ‐Dex and its ability to stimulate B cell proliferation. The concentrations of anti‐μ‐Dex (10 μg/ml) that led to the highest increase in [Ca2+]i resulted in thymidine incorporation that was no greater than that of medium control, whereas 0.01 to 0.1 μg/ml stimulated significant thymidine incorporation with 50% lower levels of stimulation of [Ca2+]i. These data demonstrate that anti‐μ‐Dex is a potent activator of human B lymphocytes, is effective even at ng/ml concentrations which over a 2‐h time period do not induce detectable modulation of sIg, and its stimulation of B cells into G1 and S may not be directly related to its ability to stimulate increases in levels of [Ca2+]i.
Abnormal behavior of γ‐committed B lymphocytes probed by a lymphocyte blastogenesis inhibitory factor in autoimmune MRL mice
Authors: Sugimura Kazuhisa , Wada Yumiko , Kimura Tatsuji , Ohno Takeshi , Kobayashi Seiichi , Azuma Ichiro 
Published: March 2007

AbstractRecently, we have characterized a lymphocyte blastogenesis inhibitory factor (LBIF) which was purified from the culture supernatant of a human histiocytic lymphoma U‐937 (Sugimura, K. et al., Eur. J. Immunol. 1989. 19: 1357). In this study, we investigated the effect of LBIF on the antibody production of autoimmune MRL mice in vitro. We demonstrated here that (a) LBIF inhibited the IgM, IgG and IgA antibody responses of lipopolysaccharide (LPS)‐stimulated spleen cells of normal BALB/c mice, (b) in the case of old autoimmune MRL/Mp‐lpr/lpr (MRL/l) and MRL/Mp‐+/+ mice, however, LBIF inhibited IgM and IgA but not IgG responses of LPS‐stimulated spleen cells, (c) the antibody production of all IgG subclasses, IgG3, IgG1, IgG2b and IgG2a, was not sensitive to LBIF inhibitory activity in these autoimmune mice, (d) in young MRL mice (3–5‐week‐old MRL/l), which were phenotypically normal, LPS‐induced antibody production of all isotypes (IgM, IgG and IgA) was strongly inhibited by LBIF as shown in normal BALB/c mice and (e) in the case of 7‐week‐old MRL/l the insensitivity to LBIF was concomitant with the appearance of γ+ B lymphocytes.Thus, by employing LBIF as a probe, this study showed a correlation between the pathogenesis of MRL autoimmune disease and the lack of LBIF sensitivity of hyperactive B lymphocytes and suggested that the intrinsic abnormality of autoimmune MRL B lymphocytes might be confined to γ‐ but not μ‐ or α‐committed B cells.
Immunochemical characterization of antigenic domains on human interferon‐β: spatially distinct epitopes are associated with both antiviral and antiproliferative activities
Authors: Redlich Philip N. , Grossberg Sidney E. 
Published: March 2007

AbstractThe use of a panel of monoclonal antibodies (mAb) raised against recombinant (serine‐17) human interferon‐β (rHuIFN‐βser) has permitted the identification of three epitopes on HuIFN‐β, designated as sites I, II and III, based solely on functional differences, i.e., the neutralization of antiviral and antiproliferative activities of natural and recombinant HuIFN‐β (Redlich, P. N. and Grossberg, S. E., J. Immunol. 1989. 143: 1887). Site I‐ and II‐directed mAb possessed neutralizing activity whereas none was noted by mAb recognizing site III. To characterize further these epitopes by immunochemical means, we studied their (a) spatial relationship by competitive binding assays, (b) antigenic structure by Western blotting, and (c) sensitivity to chemical modification by the measurement of mAb reactivity after radioiodination. Competitive antibody binding studies revealed site II to be spatially distinct from sites I and III. Furthermore, site I‐ and II‐directed mAb could easily recognize rHuIFN‐βser on a Western blot, suggesting that both these epitopes are primarily sequential in structure or denaturation resistant. Chemical modification by radioiodination, which did not alter the biologic activity of rHuIFN‐βser, had likewise little effect on mAb reactivity to site I; however, reactivity to site II was diminished and reactivity to site III was minimal following the radioiodination process. Both site I‐ and II‐directed mAb inhibited the binding of 125I‐rHuIFN‐βser to intact Daudi cells, suggesting that inhibition of receptor binding is their mechanism of neutralization. Thus, we conclude that epitopes I and II, which are associated with both antiviral and antiproliferative activities of rHuIFN‐β, are spatially and immunochemically distinct.
Inverse relationship of CA2+ mobilization and cell proliferation in CD8+ memory and virgin T cells
Authors: Schlunck Tilman , Schraut Winfried , Riethmüller Gert , Ziegler‐Heitbrock H. W. Löms 
Published: March 2007

AbstractMemory T cells can now be defined with various monoclonal antibodies but little is known about the functional properties of these cells as compared to virgin T cells. We have studied Ca2+ mobilization and proliferation of memory and virgin cells in both the CD4 and CD8 subsets in response to phytohemagglutinin.Using two‐color fluorescence (yellow, red) for cell surface staining combined with two‐color fluorescence for the Ca2+ chelator indo‐1 (violet, blue) we can demonstrate that CD8+UCHL1+ memory cells exhibit a 1,5‐fold higher influx than the CD8+UCHL1− virgin cells. The same pattern was obtained when CD8 memory and virgin cells were defined by a reciprocal marker (Leu‐18) indicating that the higher response of memory CD8 cells is independent of the monoclonal antibody used to identify the cells. For the respective CD4 subsets no such clear‐cut pattern of Ca2+ influx was evident.Analysis of proliferation in both subsets indicates that CD8+UCHL1− cells strongly proliferate in response to PHA, while CD8+UCHL1+ memory cells show only a minimal response with the average cpm values being 6‐fold lower. In some instances no proliferation at all was detectable in the CD8+UCHL1+ cells. Identification of the subsets by reciprocal markers confirmed the lower proliferative response in the CD8 memory cells. Hence, within the CD8 compartment the memory cells, after phytohemagglutinin stimulation, exhibit a high Ca2+ mobilization but a low to absent proliferation, while the converse is true for the naive cells. These data show that (a) Ca2+ mobilization and proliferation are inversely correlated and (b) an initially vigorous response of memory cells may be subject to negative control mechanisms.
Expression of T cell receptor Vγ5 in the adult thymus of irradiated mice after transplantation with fetal liver cells
Authors: Ogimoto Masaro , Yoshikai Yasunobu , Matsuzaki Goro , Matsumoto Koji , Kishihara Kenji , Nomoto Kikuo 
Published: March 2007

AbstractT cell receptor (TcR) γ/δ displays limited diversity and its diversity is distinct in different stages of ontogeny and in different anatomical sites. The Vγ5 and Vδ1 gene products are preferentially expressed on the early fetal thymocytes and on Thy‐1+ dendritic epidermal cells, whereas the Vγ4 and Vδ5 gene products are abundantly expressed on the adult thymocytes. To elucidate whether the developmentally ordered appearance of thymocytes expressing TcR γ/δ is dependent on the source of T cell precursors or is controlled by the thymic environment where T cells develop, we compared the expression of Vγ5 on the early‐appearing thymocytes between irradiated mice after transplantation with fetal liver (FL) cells and those after transplantation with bone marrow (BM) cells. Sequential appearance of thymocyte subpopulations was observed in the thymus of radiation FL chimeras similar to that seen in radiation BM chimeras. A substantial number of thymocytes bearing Vγ5 appeared in the thymus at the early stage of radiation FL chimeras, whereas few, if any, of such Vγ5‐bearing thymocytes were detected in the thymus at any stage of radiation BM chimeras. These results suggested that the ordered expression of Vγ repertoire may depend on the origin of the T cell precursors but not on the thymic environment.
Role of interleukin 2 receptor β chain in initiating anti‐CD3 and interleukin 2‐induced proliferation of human resting T cells
Authors: Moiré Nathalie , Calvo Charles‐Félix , Métivier Didier , Perrot Jean‐Yves , Vaquero Catherine , Hatakeyama Masanori , Senik Anna 
Published: March 2007

AbstractWe have examined the role of isolated interleukin 2 receptor (IL 2R) β chains expressed by human resting T cells in the early period of primary T cell activation induced by soluble OKT3 monoclonal antibody (mAb) and exogenous IL 2. In the initial 3‐day‐stimulation phase, high IL 2 concentrations were required, in association with soluble OKT3 mAb, to induce the formation of IL2R α/β heterodimers, while later, low IL2 concentrations were sufficient to promote cell growth. When added during the initial phase, TU27 mAb directed at the IL2 binding site of IL2R β chain substantially inhibited the appearance of functional high‐affinity IL2R. Lo‐Tact‐1 mAb directed at the IL2 binding site of the IL2R α chain had only a marginal effect. Strong induction of IL2R α mRNA occurred within 3 days upon OKT3 and IL2 stimulation even in the presence of Lo‐Tact‐1 mAb, but not in the presence of TU27 mAb. OKT3 alone failed to induce significant IL2R α gene transcription and that induced by IL2 alone was very weak. The constitutive expression of IL2R β mRNA was visualized in resting T cells. It remained at a rather stable level, at least during the initial stimulation period which was examined herein.Given the fact that OKT3 alone was ineffective in up‐regulating IL2R β mRNA expression and that pre‐incubation of the cells with OKT3 alone did not allow them to respond to high concentrations of IL2, it is highly probable that isolated IL2R β chains constitutively expressed by CD8+ T cells (the main reactive cells in this system) are primarily responsible for the initial interaction of IL2 with these cells. Such an interaction will result in the formation of high‐affinity IL2R and in the initiation of cell proliferation provided that a CD3‐derived co‐signal is simultaneously delivered to the cells.
5‐Azacytidine inhibits the lpr gene‐induced lymphadenopathy and acceleration of lupus‐like syndrome in MRL/MpJ‐lpr/lpr mice
Authors: Yoshida Haruyoshi , Yoshida Michiko , Merino Ramon , Shibata Takanori , Izui Shozo 
Published: March 2007

AbstractMRL/MpJ‐lpr/lpr mice spontaneously develop a lupus‐like autoimmune disorder characterized by massive proliferation of T cells and rapidly fatal immune complex glomerulonephritis. We evaluated the therapeutic effect of 5‐azacytidine (5AC), a cytidine analogue known as an inhibitor of DNA methylation, in MRL/MpJ‐lpr/lpr mice. Intraperitoneal injection of 5AC (50 μg, twice a week) starting from 6 weeks of age retarded the development of lymphadenopathy and autoimmune syndrome. Its beneficial effects included: (a) increased life‐span, (b) diminution of lymphadenopathy and splenomegaly, (c) reduction in circulating levels of autoantibodies such as anti‐DNA and rheumatoid factors, and (d) suppression of lupus glomerulonephritis. However, similar treatment in BALB/c mice did not affect the development of IgG anti‐human IgG antibody responses. These results suggest that the protective effect of 5AC is related to the inhibition of the lpr gene‐induced T cell proliferation, thereby suppressing the autoimmunity‐accelerating effect mediated by the lpr gene.
The requirement of intrathymic mixed chimerism and clonal deletion for a long‐lasting skin allograft tolerance in cyclophosphamide‐induced tolerance
Authors: Eto Masatoshi , Mayumi Hisanori , Yoshikai Yasunobu , Nishimura Yousuke , Nomoto Kikuo 
Published: March 2007

AbstractMechanisms of cyclophosphamide (CY)‐induced tolerance were studied. When C3H/He Slc (C3H; H‐2k, Mls‐1b) mice were primed i.v. with 1 × 108 viable spleen cells from H‐2‐identical AKR/J Sea (AKR; H‐2k, Mls‐1a) mice and treated with 200 mg/kg of CY 2 days later, a long‐lasting skin allograft tolerance to AKR was established. When [C57BL/6 Sea (B6; H‐2b, Mls‐1b) × AKR]F1 (B6AKF1) cells were used as the tolerogen, however, only a moderate, but not long‐lasting, skin tolerance to AKR was observed.In the C3H mice treated with AKR cells and CY, the intrathymic clonal deletion of Vβ6+ T cells, which are strongly correlated with reactivity to Mls‐1a antigens, was observed in the chimeric thymus on day 35, although neither the clonal deletion of Vβ6‐bearing T cells nor the mixed chimerism was observed in the thymus on day 14. In the C3H mice treated with B6AKF1 cells followed by CY, however, neither the clonal deletion of Vβ6+ T cells nor the mixed chimerism was observed in the thymus throughout the test period. In the lymph nodes of the C3H mice treated with AKR cells and CY, only CD4+Vβ6+ T cells, but not CD8+Vβ6+ T cells, had selectively decreased by day 14, and they were hardly detectable on day 35. The selective decrease of CD4+Vβ6+ T cells in the lymph nodes was also observed by day 14 when B6AKF1 cells were used as the tolerogen, although CD4+Vβ6+ T cells gradually increased on day 35, at which time almost all skin grafts from AKR had already been rejected. These results strongly support the necessity of the intrathymic mixed chimerism and clonal deletion of donor‐reactive T cells for a long‐lasting skin allograft tolerance in CY‐induced tolerance.
Functional markers of the major histocompatibility gene complex of snakes
Authors: Farag Magda Adly , Ridi Rashika El 
Published: March 2007

AbstractIn optimal seasonal conditions, outbred adult snakes Psammophis sibilans displayed the major immunological functions related, in mammals, to the presence of the major histocompatibility gene complex (MHC). Thus, out of 30 snake random pairs that exchanged skin transplants 72.9% rejected their allograft in an acute or subacute manner. Strongly significant proliferative response was recorded in 67.3% of 168 separate one‐way mixed leukocyte reaction (MLR) cultures. Lymphocytes from 6/11 snakes immunized by skin allografting displayed, after secondary stimulation in vitro, cell‐mediated lympholysis (CML) in vitro of 51Cr‐labeled lymphoblasts derived from the donor snake. Finally, cytotoxic alloantibodies were readily generated after snake priming with skin allograft and blood cells.Snakes did not only exhibit the major cell‐ and humoral‐mediated immune functions, but these functions appeared to be linked with the degree of MLR disparity. Thus, animals with different MLR rejected skin allografts acutely and produced cytotoxic effector cells. In contrast, MLR‐identical animals rejected the skin allograft of their partner chronically and failed to produce killer cells in CML. This significant positive correlation between MLR disparity, graft rejection and CML suggests that the responsible antigens are encoded, as in other vertebrates, by the same genetic system, the MHC.
Resistance to murine cutaneous leishmaniasis is mediated by TH1 cells, but disease‐promoting CD4+ cells are different from TH2 cells
Authors: Moll Heidrun , Röllighoff Martin 
Published: March 2007

AbstractA limiting dilution system has been used for quantitative analysis of antigen‐reactive T cells producing interleukin (IL)2, IL4 and interferon (IFN)‐γ in the course of murine infection with Leishmania major. The precursor frequencies of CD4+ cells with the potential for production of IFN‐γ, which has been associated with TH1 cells, are much higher in resistant than in susceptible mice, whereas the reverse is found for CD4+ cells secreting IL4 which have been classified as TH2 cells. Our results allow a better understanding of the relative contribution of these cell types at various stages of disease and can be summarized as follows: (a) secretion of IL4 can be demonstrated in short‐term clonal cultures of CD4+ cells from L. major‐infected mice, (b) CD4+ cells releasing IL2, suggested to be a characteristic of TH1 cells that predominate in resistant mice, can also be detected in susceptible mice at any time of infection, (c) both IL2 and IL4 are released by the progeny of individual T cells from susceptible mice and (d) the kinetics of precursor frequencies in genetically susceptible mice protected against the disease by prophylactic treatment are different from those of congenitally resistant mice, thus indicating that the development of lymphokine‐producing T cells and the establishment of protective immunity may be regulated differently in those mice. The data suggest that resistance to disease is correlated with the presence of IFN‐γ‐producing TH1 cells, while susceptibility is associated with CD4+ cells that do not segregate into the TH1 or TH2 subset but display an overlapping pattern of lymphokine activities.
Participation of a dominant cytotoxic T cell population defined by a monoclonal antibody in syngeneic anti‐tumor responses
Authors: Matsubayashi Yuji , Hirama Toshiyasu , Morioka Atsuo , Iwashiro Michihiro , Masuda Tohru , Uchino Haruto , Takeshita Sunao , Yamagishi Hideo , Udono Heiichiro , Mieno Masahiro , Nakayam Eiichi , Shiku Hiroshi , Uenaka Akiko , Kuribayashi Kagemasa 
Published: March 2007

AbstractCytotoxic T lymphocyte (CTL) clones against a syngeneic Friend virus‐induced erythroleukemia (FBL‐3) were generated in C57BL/6 (B6) mice. A monoclonal antibody (mAb, N9‐127) was then raised from spleen cells of a B6 mouse immunized syngenically against one of these CTL clones. This mAb detected the epitope (127Ep) of the T cell antigen receptor (TcR) on the immunizing CTL clone in tests of immunoprecipitation, specific blocking and proliferation, and induction of TcR‐mediated nonspecific lysis of the clone. In addition, more than 10% of the FBL‐3‐specific CTL clones isolated independently from B6 mice were 127Ep+. Further investigations revealed that up to 30% of B6 anti‐FBL‐3 T cell blasts from mixed lymphocyte tumor cell cultures were positive for this epitope, and that its expression was confined to CD8+ T cells. This epitope was not detected in naive lymphoid cells from the spleen, lymph nodes or thymus or in T cell clones specific for tumors other than FBL‐3. The FBL‐3‐specific CTL clones were next grouped into 127Ep+ and 127Ep− clones. Sequence analyses of the CTL clone used for immunization showed the rearrangements of Vα1Jα112‐2 and Vβ10Dβ2.1Jβ2.7. Southern blot analysis of all the 127Ep+ CTL clones examined showed the same DNA rearrangement bands of both the TcR α and β genes. These findings suggested that mAb N9‐127 recognized the shared determinant of the TcR molecule which was expressed by the dominant CTL population in the response to FBL‐3.
The neutrophil‐activating proteins interleukin 8 and β‐thromboglobulin: in vitro and in vivo comparison of NH2‐terminally processed forms
Authors: van Damme Jo , Rampart Marc , Conings René , Decock Benny , van Osselaer Nancy , Willems Jean , Billiau Alfons 
Published: March 2007

AbstractIsolation of the human neutrophil activating protein (NAP) interleukin 8 (IL 8) from leukocytes has revealed that it is structurally related to β‐thromboglobulin (βTG) from platelets. Both these proteins occur as natural mixtures of multiple forms, differing from each other by unequal truncation at the NH2 terminus. In this study we have compared IL8 and βTG forms for in vitro and in vivo neutrophil activation. In contrast to IL8, none of the βTG forms were found to exert granulocyte chemotactic activity in vitro, as measured in the agarose assay. However, fractions rich in the most extensively processed forms of βTG (e.g. NAP‐2) as well as pure NAP‐2 did induce lactoferrin release from granulocytes, whereas fractions containing only the longer forms (e.g. connective tissue‐activating peptide III) were inactive. In order to observe this in vitro effect, about 10‐fold less IL8 (10 nM) than NAP‐2 was required. In the presence of a vasodilatator substance low doses (2–20 pmol) of IL8 and the shorter forms of βTG caused granulocyte accumulation and plasma leakage in rabbit skin whereas the longer forms of βTG again failed to do so. Finally, granulocytosis induction following i.v. injection was found to occur with NAP‐2. At the maximal dose tested (250 pmol), this in vivo effect of NAP‐2 was less pronounced than that of IL8. In the case of IL8, NH2‐terminal processing did not seem to affect granulocyte stimulatory activity. It should be noted, however, that the extent of processing of IL8 is less than that occurring with βTG. It can be concluded that the platelet factor βTG, structurally related to the monokine IL8, can also play a role in neutrophil activation during inflammatory reactions.