摘要:

AbstractThe accessory cell requirements in lectin‐dependent triggering and growth of unprimed Lyt‐2−T lymphocytes were analyzed by quantitatively comparing the ability of small B cells and peritoneal macrophages to either induce reactivity to growth factors or support growth.Lightly or nonirradiated small B cells were 15 to 30‐fold less efficient as compared to T cell‐depleted peritoneal cell populations, in the support of lectin‐stimulated Lyt‐2−T cell proliferation. In contrast, lightly irradiated small B lymphocytes were quantitatively as efficient as macrophages in mediating lectin‐driven Lyt‐2−T cell proliferation, if relevant supernatants were added into culture. Finally, supernatants derived from cultures where T‐small B cell ratios were optimal for growth of responder Lyt‐2−lymphocytes were two orders of magnitude less efficient than conditioned medium obtained from cultures containing optimal T‐macrophage ratios, in their ability to support growth of activated T cells.We conclude from these experiments that: (a) in contrast to cytolytic T cell precursors, lectin‐dependentinductionof unprimed Lyt‐2−T lymphocytes requires accessory cells; (b) small B cells and macrophages are equally competent in this respect; and (c) growth support by small B cell populations is due to contamination by macrophages which are the only cell type performing this function. We therefore interprete reports on Lyt‐2−T cell proliferation upon stimulation with high numbers of small B cells as a two‐step process: “presentation” and induction of T cells which is essentially B cell dependent, and factor pr

ISSN:0014-2980    

DOI:10.1002/eji.1830150902

出版商:WILEY‐VCH Verlag GmbH    

年代:1985

数据来源: WILEY

摘要:

AbstractA cDNA library of phosphorylcholine (PC)‐specific suppressor T hybridoma, 29‐C‐6, was constructed. By differential colony hybridization, 68 colonies were selected which hybridized with mRNA probes of two PC‐specific suppressor T hybridomas, 29‐C‐6 and 09‐M‐24–8, but not with those of BW5147. A hybridization translation assay revealed that only one combination of translation products of cDNA clones, p6–1 and p6–5, showed strong PC‐T cell suppressor factor (TsF) activity. Sequence analysis showed that p6–5 contained a specific cDNA sequence of about 800 base pairs (bp) while p6–1 had a 190 bp poly(A) sequence insert.When total poly(A)+RNA of 29‐C‐6 was hybridized with a p6–1 filter alone the recovered mRNA was capable of producing PC‐TsF. However, when the total poly‐(A)+RNA was hybridized with a p6–1 filter combined with a p6–5 filter, the mRNA eluted from the p6–1 filter was not able to produce PC‐TsF, suggesting that the depletion of p6–5 specific mRNA from p6–1‐binding poly(A)+RNA led to a complete abolishment of the capability to produce PC‐TsF.Furthermore, p6–5 hybridizing mRNA could successfully restore the p6–1‐binding poly(A)+RNA depleted of p6–5‐specific mRNA, and translation products of both RNA mixtures showed strong PC‐TsF activity. These results suggest that PC‐TsF is not a single polypeptide chain, but is composed of at least two distinct polypeptide chains, and also that p6–5 contains a cDNA sequence enc

ISSN:0014-2980    

DOI:10.1002/eji.1830150903

出版商:WILEY‐VCH Verlag GmbH    

年代:1985

数据来源: WILEY

摘要:

AbstractEarlier studies have indicated that Clq, the first subcomponent of complement component C1, is bound to lymphocytes via specific Clq receptor sites. We have recently shown that adherent guinea pig peritoneal exudate macrophages express specific receptors for Clq (Veerhuis, R. et al.,Immunology1985.54: 801). The present studies were performed to determine whether binding of125I‐labeled human Clq (125I‐Clqhu) to adherent guinea pig peritoneal exudate macrophages would also result in ingestion and subsequent degradation of125I‐Clqhu. The binding of125I‐Clqhuto adherent peritoneal macrophages at 4°C is inhibited fully not only by Clqhuand guinea pig Clq (Clqgp) but also by pepsin fragments of Clqhu. The amount of trichlo‐roacetic acid nonprecipitable radioactivity that appeared in the supernatant was used as a measure for the degradation of125I‐Clqhu.125I‐Clqhuis degraded initially into fragments of 25 kDa, after which it is degraded further into small molecular weight peptides. Ingestion of125I‐Clq by the macrophages occurs before the125I‐Clq is degraded.In the presence of limited amounts of soluble aggregates of guinea pig IgG2(AIgG), a known activator of C1, part of the Clq is bound to the AIgG and all of the AIgG in turn is bound to the cellular Fc receptors leading to an enhanced binding of125I ‐Clq to the cells, a binding that was maximal at near equimolar concentrations of125I‐Clqhuand131I‐AIgG. In the presence of a 30‐fold excess of AIgG, however, only a small percentage of the AIgG binds to cellular Fc receptors and the interaction of Clq with its receptor is decreased due to competitive inhibition. The results presented in this report thus suggest that free Clq may be eliminated by specific interaction with Clq receptors present on circulating and tissue phagocytoses and, in addition, that in the presence of immune complexes modulation of elimination

ISSN:0014-2980    

DOI:10.1002/eji.1830150904

出版商:WILEY‐VCH Verlag GmbH    

年代:1985

数据来源: WILEY

摘要:

AbstractThe ability of two antibodies, one specific for the a chain, p180, and the other for the β chain, p95, of the human lymphocyte function‐associated (LFA‐1) antigens, to inhibit T cell function was measured. Both antibodies inhibited T cell‐mediated lysis of virus‐infected target cells and of K562 cells. Only the anti‐β chain antibody inhibited natural killer cell lysis of K562. The antibodies inhibited cytotoxic T lymphocyte cell (CTL) lysis of HLA‐mismatched target cells in the presence of concanavalin A at 6.25–12.5 μg/ml, but at higher doses of Con A no inhibition was seen. When the lytic process was divided into calcium‐independent (adherence) and ‐dependent (lysis) steps the antibodies were found to block at the initial step of conjugate formation. The effects of these antibodies on T cell proliferative responses showed that responses to antigens, alloantigens, mitogens and anti‐CD3 (UCHT1) antibody were greatly inhibited. All of these responses are adherent cell dependent and proliferation of adherent cell‐depleted mononuclear cells to Sepharose‐coupled UCHT1 was not inhibited by anti‐LFA‐1 antibodies. Proliferation to paired anti‐CD2 (T11) antibodies was also only weakly inhibited. Release of interferon‐γ by CTL on contact with target cells was also inhibited by anti‐LFA antibody. These results are evidence that the LFA antigen is necessary for a nonspecific interaction with antigen ‐presenting cells that is essential for activation of T cells

ISSN:0014-2980    

DOI:10.1002/eji.1830150905

出版商:WILEY‐VCH Verlag GmbH    

年代:1985

数据来源: WILEY

摘要:

AbstractLabeled monomeric and polymeric (pIgA) mouse monoclonal IgA were injected intravenously into mice which were either sequentially bled for plasma turnover studies of IgA, or cannulated at their common bile duct, with excluded gallbladder, for quantitation of plasma‐to‐bile transport of pIgA. Our data show that mice do display a relatively high rate of biliary transport of plasma pIgA (22–28% of the injected125I‐labeled pIgA over 3 h), which accounts for ∼90% of the total amount of pIg A (8.8 mg/kg/day) daily delivered by hepatic bile into the duodenal fluid of this species. However, in mice the absolute biliary output of pIgA does not exceed that of IgG (9.5 mg/kg/day) and the kinetics of the hepatobiliary transport of plasma PIgA appear to be slower than in the rat. Furthermore, as plasma survival studies of125I‐labeled pIg A yielded a plasma turnover of pIgA averaging 20.6 mg/kg/day, it can be approximated that the hepatobiliary pathway contributes for only 38% to the elimination of intravascular pIgA from mouse plasma, a figure to be compared to 89.8% in the rat and ∼ 8.9% in man. We conclude that internal catabolism plays a dominant role in the clearance of intravascular pIgA in the mouse which appears as a model intermediate between rats and humans. Supporting this conclusion, serum pIgA two days after common bile duct ligation in 6 mice was increased by 2.5‐foldvs.>14‐fold in ligated rats and 1.1‐fold in humans with complete

ISSN:0014-2980    

DOI:10.1002/eji.1830150906

出版商:WILEY‐VCH Verlag GmbH    

年代:1985

数据来源: WILEY

摘要:

AbstractLy‐2+CBA mouse T lymphocytes stimulated with concanavalin A in limiting dilution culture produce clones of cytotoxic T lymphocytes (CTL) which, although initially specific, eventually lyse a wide range of target cells. The nature of the recognition system for this apparently “nonspecific” cytolysis was examined using a range of tumor cells as labeled targets and as cold target inhibitors. Most syngeneic and allogeneic murine tumor cells were lysed but the degree of lysis varied, even for different sublines of the same tumor. All tumor cells cold target inhibited their own lysis, and cross‐inhibited lysis of other targets to varying degrees. The recognition stage of “nonspecific” cytolysis appeared to be independent of target cell H‐2 expression; some H‐2‐negative murine target cells were lysed and some were not, but all gave cold target inhibition of “nonspecific” cytolysis. Xenogeneic tumor cells were resistant to lysis, but some nevertheless gave cold target inhibition of the “nonspecific” cytolysis of murine targets. A study of the specificity of cold target cross‐inhibition revealed two distinct patterns of recognition which existed simultaneously in “nonspecific” CTL; one was like that of natural killer cells and was directed to targets such as YAC‐1, the other was distinct from that of natural killer cells and was directed to targets such as P815. Thus, murine CTL may express three distinct receptors, the clonally distributed, H‐Zrestricted, antigen‐specific T cell receptor and two different “broad

ISSN:0014-2980    

DOI:10.1002/eji.1830150907

出版商:WILEY‐VCH Verlag GmbH    

年代:1985

数据来源: WILEY

摘要:

AbstractAlthoughxid/Y mice fail to make a detectable primary antibody response to a variety of antigens such as Type III pneumococcal capsular polysaccharide (SIII), 2,4,6‐trinitrophenyl (TNP)‐Ficoll, pneumococcal C carbohydrate, group A streptococcal vaccine and several kinds of related antigenic determinants such as phosphorylcholine (PC) and N‐acetyl‐glucosaminyl (GlcNAc), even when the latter are coupled to hemocyanin (Hy), they do show: (a) an antigen‐dependent development of splenic B cells which can act as successful, productive fusion partners for SP2 cells giving hybridomas making monoclonal anti‐SIII, anti‐PC, anti‐GlcNAc, anti‐TNP, etc., and (b) an antigen‐dependent appearance of antigen‐binding plasmablasts in their spleens. The frequencies of specific B cells arising inxid/Y males with either of these properties are of the same order of magnitude as those found in immunocompetentxid/Y female littermates. Further, both PC‐Hy and GlcNAc‐Hy primexid/Y andxid/X mice for quantitatively and qualitatively similar secondary responses. All three of these expressions of a specific, primary response occur inxid/Y mice in the absence of any rise in circulating antibodies.The properties of successful, productive normal fusion partners leading to secretory hybridoma lines are unknown. Thus we cannot decide whether the antigen‐binding plasmablasts that arise inxid/Y mice can also play the role of productive fusion partners. Neither do we know whether the development of specific IgM and IgG3plasmablasts inxid/Y mice after antigen stimulation is an abnormality reflecting thexidmutation. It cannot be excluded that the development of productive fusion partners, of nonsecretory plasmablasts and of memory cells are all interrelated and reflect a process that also normally occurs inxid/Y, X/X and X/Y mice following similar immunization regimens. It is tempting to speculate that such cells initially responding may lag in the development of normal secretory mechanisms and that the “transformed” fusion partner

ISSN:0014-2980    

DOI:10.1002/eji.1830150908

出版商:WILEY‐VCH Verlag GmbH    

年代:1985

数据来源: WILEY

摘要:

AbstractSJL mice exhibit a strain‐specific age‐dependent delay in the maturation of delayed‐type hypersensitivity (DTH) responsiveness. They do not attain “adult” levels of DTH responsiveness until the 10th week of age, which is 4 to 6 weeks later than the other strains of mice tested. In this report we demonstrate that spleen cells, resident peritoneal cells and thioglycollate‐elicited peritoneal exudate cells are all able to transfer DTH responsiveness from naive 12‐week‐old DTH responders to 6‐week‐old nonresponders. Transfer prior to immunization was more efficient at eliciting a response than transfer after immunization. As few as 5 ± 104cells from 12‐week‐old SJL mice can adoptively transfer responsiveness to unresponsive 6‐week‐old animals. The active cell was found to be adherent, radiation (2000 rds) resistant, I‐A+, Thy‐1−and Mac‐l+. I‐A compatibility between the adoptively transferred population and the nonresponder mice is required. These data suggest that young adult SJL mice lack a functional population of antigen‐presenting cells specific for DTH and that the appearance of t

ISSN:0014-2980    

DOI:10.1002/eji.1830150909

出版商:WILEY‐VCH Verlag GmbH    

年代:1985

数据来源: WILEY

摘要:

AbstractRecently, the regions of myoglobin, which are recognized by T cells (T sites), were localized by a comprehensive synthetic strategy in which uniform synthetic overlapping peptides encompassing the entire protein chain were examined for stimulation of T cell proliferative activity. In this study, we report about the proliferative response to these peptides, as well as to the native protein, of lymph node cells from mice primed with the overlapping peptides either individually or in a mixture. Some, but not all, of the T site‐containing peptides were effective in priming for an anti‐myoglobin T cell response. Further, several peptides, which were highly immunogenic as free synthetic peptides, were not associated with any of the known T sites in this protein. Thus, the pattern of T cell recognition following priming with the overlapping peptides differs from the pattern observed when the native protein is the priming antigen. If antigen processing proceeds via fragmentation, then only those regions containing T sites would be expected to be effective in priming for a T cell response to the intact protein and, conversely, highly immunogenic peptides would correspond to T sites of the protein. Therefore, these findings indicate that the current concept of antigen fragmentation as a prerequisite for its presentation must be reappraised. We suggest that, in the presentation of a protein antigen, the protein is recognized predominantly intact and that the crucial aspects of presentation are determined by interaction with the cell membrane which trigger cellular activating eve

ISSN:0014-2980    

DOI:10.1002/eji.1830150910

出版商:WILEY‐VCH Verlag GmbH    

年代:1985

数据来源: WILEY

摘要:

AbstractI‐J originally mapped within the murine major histocompatibility complex (H‐2) between the EBand Ea, loci using intra‐H‐2 recombinants. Cloning of this segment of H‐2 shows no DNA that can be ascribed to I‐J. Various hypotheses have attempted to explain this dilemma. One hypothesis attributes a chromosome 4 locus with I‐Jkexpression. This hypothesis requires the AKR/J and A/WySn mouse strains to be I‐Jknegative. In the present report we show that AKR/J spleen cells express I‐Jksurface molecules and that both the AKR/J and A/WySn mouse strains produce functional I‐Jk‐bearing suppressor factors to poly(Glu50Tyr50). Our data imply that mapping of I‐J‐determining genes to chro

ISSN:0014-2980    

DOI:10.1002/eji.1830150911

出版商:WILEY‐VCH Verlag GmbH    

年代:1985

数据来源: WILEY