摘要:

AbstractMost helminth parasites induce a strong IgE antibody and elevated eosinophil response in their mammalian hosts and a number ofin vitrostudies have suggested that IgE, possibly in association with eosinophils, may be an essential element of the host protective immunity against helminth infections. To assess the role of IgE in protective immunity, we examined the effect of suppressing the IgE antibody response on rat immunity toSchistosoma mansoni.Suppression was achieved in neonates by injections of rabbit anti‐ϵ chain γ‐globulins, control rats received injections of unspecific γ‐globulins. IgE suppression caused a marked reduction of the inflammatory reaction that developed in the skin of immune rats at the site of a cercarial challenge: the early (30 to 60 min) wheal and flare reaction was abolished, and the late cutaneous reaction (6 to 18 h) associated with intense pruritus, edema and local eosinophilia was greatly reduced. This shows that IgE was critical to the recruitment of effector cells and molecules in the skin during the first 24 h following parasite invasion.Worms were recovered 18 to 30 days after a primary infection and 18 days after a challenge infection from IgE‐suppressed and control rats. IgE‐suppressed rats cured a first infection as rapidly as the control rats; however, they were two to three times less efficient than the controls at eliminating a second or a third challenge. These observations demonstrate that IgE antibodies are essential for the full development of rat acquired protective immunity againstSchisto

ISSN:0014-2980    

DOI:10.1002/eji.1830160602

出版商:WILEY‐VCH Verlag GmbH    

年代:1986

数据来源: WILEY

摘要:

AbstractThe lysis by human and murine anti‐HLA cytolytic T lymphocytes (CTL) of murine cells expressing class I HLA molecule after gene transfection has been studied using two different murine cells: LMTK−and P815‐HTR‐TK−. Weak but significant HLA‐A11‐specific lysis was found occasionally with human CTL on the HLA‐A11+L cells. On the contrary, P815‐A11 or P815‐A2 cells were lysed strongly and specifically by HLA‐A11 or HLA‐A2‐specific human CTL. The T8+T4−phenotype of the effector cells was confirmed and the reaction was inhibited by anti‐HLA class I monoclonal antibodies. Despite their higher sensitivity to human CTL, the P815‐HLA+cells did not express higher levels of HLA antigens than L cells, and the presence or the absence of human β2microglobulin was irrelevant. Anti‐human LFA‐1 antibodies abrogated the lysis of P815‐A11+cells showing that the LFA‐1 receptor which is apparently lacking on the L cell surface was on the contrary expressed on P815 cells. On the other hand, murine anti‐HLA CTL have been prepared by immunizing mice against syngeneic HLA‐A11+L cells. They lysed very efficiently and specifically these cells, but appeared completely devoid of activity against human HLA‐A11 target cells. This barrier was apparently due to the H‐2 restriction of these H‐2kanti‐HLA murine CTL, as shown by their inability to lyse allogeneic H‐2dcells expressing HLA‐A11, and by the blocking of their activity by anti H‐2kantibodies. By contrast, xenogeneic anti‐HLA CTL obtained by immunizing murine lymphocytes against human cells lysed both human and murine HLA+cells but they reacted with a monomorphic epitope of the HLA molecule in a nonrestricted way. These results show that (a) human cells lyse very efficiently P815 murine cells expressing HLA class I antigens; (b) the higher sensitivity of P815 cells compared to L cells is probably due to the presence of a LFA‐1 receptor on these cells; (c) a class I molecule of human origin can be seen as an H‐

ISSN:0014-2980    

DOI:10.1002/eji.1830160603

出版商:WILEY‐VCH Verlag GmbH    

年代:1986

数据来源: WILEY

摘要:

AbstractThe frequency of specific cytotoxic T lymphocytes (CTL) precursors in the total CTL pool was analyzed in a lectin‐driven limiting dilution system. We found that up to 10% of the expressed CTL repertoire in a normal mouse is “specific” for a given allogeneic H‐2 haplotype. Split‐well analysis under clonal conditions demonstrates that the antigens recognized by the effector CTL are H‐2 encoded. A high frequency of CTL “specific” for self‐H‐2 antigens was revealed in all the experiments, accounting for about 1% of the total inducible pool of CTL. These results suggest a high degree of degeneracy of H‐2 recognition by CTL and the immunocompetence of self‐H‐Zreactive CTL precurs

ISSN:0014-2980    

DOI:10.1002/eji.1830160604

出版商:WILEY‐VCH Verlag GmbH    

年代:1986

数据来源: WILEY

摘要:

AbstractFunctional studies, using mainly interleukin 2 (IL 2)‐dependent growth of human T cell lines or clones but also mixed lymphocyte cultures and mitogen T cell activation, allowed a collection of locally produced anti‐IL2 receptor monoclonal antibodies (mAb) to be classified. They fell into two groups: one with strong to moderate inhibition of IL2, the other without any detectable functional activity inin vitroassays. Direct and sequential immunoprecipitation as well as peptide mapping confirm that all the mAb recognize the same surface molecule. The parameters responsible for such functional dichotomy were characterized: the main parameter was found to be linked to the epitopic cluster recognized on the molecule by the mAb. All functional mAb pertained to a given epitopic cluster and all the nonfunctional ones to an alternative cluster. Studies on mAb receptor and IL2 receptor interactions confirmed these findings and strongly suggest that functional mAb interact with a region on the IL2 receptor identical or very close to the site of ligand‐receptor interaction. These data could facilitate the choice of mAb to be used in therapeutical approachesin vivowhen ethical objections could be overcome by appropriate commi

ISSN:0014-2980    

DOI:10.1002/eji.1830160605

出版商:WILEY‐VCH Verlag GmbH    

年代:1986

数据来源: WILEY

摘要:

AbstractThe formation of classical C3 convertase of complement and its regulation by C4b‐binding protein (C4bp) were studied using two different approaches: (a) the analysis was first carried out in fluid phase; a soluble stabilized C3 proconvertase could be assembled from C4b (or C4b‐like C4) and iodine‐treated C2 in the presence of Ni2+ions. Upon activation of this complex by C1s, a C3 convertase C4b(C4b‐like C4)‐C2a was generated which was able to cleave purified C3. C4bp dissociated both C3 proconvertase and C3 convertase, but its effect was more important on C3 convertase. (b) A model system of phospholipid vesicles has been developed to study the assembly of the C3 convertase on a membrane. Among different phospholipid mixtures tested, P‐glycerol/P‐choline vesicles were found most effective for C4b binding. Optimal conditions were determined for C4b fixation on these vesicles; bound C4b participated in the formation of a functional membrane‐associated C3 convertase. C4bp was found to bind to phospholipid vesicles with a higher affinity than C4b; it was able to dissociate the vesicle‐associa

ISSN:0014-2980    

DOI:10.1002/eji.1830160606

出版商:WILEY‐VCH Verlag GmbH    

年代:1986

数据来源: WILEY

摘要:

AbstractRecombinant interferon‐gamma (rIFN‐γ) was able to induce proliferation of human tonsillar B cells activated with suboptimal concentrations of anti‐μ antibody. The B cell growth factor (BCGF) activity of rIFN‐γ was not due to substances contaminating the IFN‐γ preparation, nor was it mediated by factors released by T cells or large granular lymphocytes following activation by rIFN‐γ. The response of B cells to rIFN‐γ peaked on day 3 of culture and rapidly declined thereafter, whereas the response of parallel anti‐μ‐activated B cell cultures to recombinant interleukin 2 (rIL2) appeared on day 3, but continued at least until day 5. In addition, B cells responsive to rIFN‐γ could be at least in part separated from those responsive to rIL2, the former being primarily contained in B cell fractions enriched for high‐density small B lymphocytes. Finally, the addition to anti‐μ‐stimulated B cell cultures of very low concentrations of rIFN‐γ potentiated the B cell proliferation promoted by rIL2.The simultaneous addition of monoclonal antibodies against IFN‐γ and T cell activation antigen to anti‐μ‐stimulated B cell cultures strongly reduced the B cell proliferative response promoted by three different crude BCGF preparations obtained by polyclonal T cell activation in mixed lymphocyte culture. However, the supernatant from a T cell clone (DP5/11) apparently free of IL2, which manifested a BCGF activity similar to that of rIFN‐γ, still maintained its ability to promote proliferation of anti‐μ‐activated B cells after complete removal of IFN‐γ.Taken together, our data indicate that although some T cell clones are able to produce a BCGF distinct from both IFN‐γ and IL2, these lymphokines account for most of the BCGF activity of supernatants obtained from polyclonal T cell populations. They also suggest that IFN‐γ and the BCGF distinct from IFN‐γ and IL 2 act primarily in the earlier phases of B cell activation and

ISSN:0014-2980    

DOI:10.1002/eji.1830160607

出版商:WILEY‐VCH Verlag GmbH    

年代:1986

数据来源: WILEY

摘要:

AbstractTwo experimental systems have demonstrated somatic variation of antigen recognition specificity of long‐term cytotoxic T cell (CTL) clones. System 1 used CTL clone BT7.4.1 with strict specificity for Kb/TNP, which had been continuously cultured for 15 months in the presence of H‐2b/TNP stimulator cells and interleukin 2. Upon removal of the TNP antigen from the cultures, 99% of the clone cells within about 10 cell divisions lost their ability to grow in the presence of antigen and interleukin 2 (lethal variants). Of the surviving 1%, about 60% retained the ability to lyse target cells in the presence of lectins but only 12% could be considered as “wild type” BT7.4.1 cells,i.e.they still specifically lysed H‐2b/TNP‐bearing target cells. The majority of the growing cells, thus, had to be considered as specificity loss variants. Several specificity loss variants were established in culture and were shown to express membrane‐bound T cell “receptor” heterodimer similar to their TNP‐specific ancester, BT7.4.1. Principally the same types of variants were generated in cultures growing in the presence of TNP antigen, although in quantitatively reduced numbers. Under these conditions the specific stimulator cells appeared to impose a significant selective advantage for “wild type” CTL since even after 15 months the cultures fully retained their specificity for the nominal antigen.In system 2, the development of cytolytic fine specificity of a panel of 42 individual Kb/TNP‐specific CTL clones was followed over a period of 8 months ofin vitroculture. At the beginning of the test, 37 of these clones exhibited significant cross‐reactivity for lysis of H‐2k/TNP target cells. This number of cross‐reactive clones continuously diminished with time and dropped to only 4 clones after 8 months in culture. All 42 clones retained their original Kb/TNP specificity and after losing their reactivity for H‐2k/TNP usually showed no decrease but rather an increase in their cytotoxic activity towards Kb/TNP target cells. Loss of H‐2k/TNP cross‐reactivity was not accompanied by loss of Lyt‐2 or of LFA‐1 surface antigens or by loss of sensitivity of the cytotoxicity to inhibition by anti‐Lyt‐2 or by anti‐LFA‐1 antibody.We conclude from these observations thatin vitrocultivated CTL clones, at least those of C57BL/6 anti‐TNP‐C57BL/6 specificity, are not stable in terms of their antigen recognition specificity. Despite this instability, their nominal cytolytic specificity can be maintained over long periods ofin vitroculture and even a maturation to increased antigen specificity is regularly observed, provided antigen is present in the cultures. We assume this indicates that maintenance of clonal specificityin vitrois a matter of antigen‐induced selection rather than a cons

ISSN:0014-2980    

DOI:10.1002/eji.1830160608

出版商:WILEY‐VCH Verlag GmbH    

年代:1986

数据来源: WILEY

摘要:

AbstractThe extent to which B cells newly formed in the bone marrow contribute to primary and secondary B cell responses was investigated. This was assessed by constructing chimeras between congenic strains of rats differing in their kappa light chain allotype. Recipient animals received 800 cGy whole body irradiation with hind limb shieldin to protect a proportion of their hemopoietic capacity. These rats then received 3 × 108kappa allotype‐marked thoracic duct lymphocytes from donors previously immunized twice with either dinitrophenylated spider crab (Maia squinada) hemocyanin (DNP‐MSH) or MSH alone. The chimeras were immunized with DNP‐MSH and the production of anti‐DNP antibody of both donor and host origin was measured. In the period immediately after immunization both newly formed host virgin B cells and donor memory B cells gave rise to substantial proportions of the anti‐DNP antibody. After this initial period, antibody production became sustained by activation of memory B cells only. The chimeras were reimmunized with DNP‐MSH at 32 days after their first immunization. There was again evidence of a brief period of both virgin and memory B cell activation followed by memory B cell activation only. Donor B cell clones remained dominant in the established response throughout the 5 months each chimera was studied. The data are interpreted as indicating two phases of B cell activation. It is suggested that the first phase where both virgin and memory B cells are activated may be associated with antigen presentation on dendritic or interdigitating cells outside follicles. It is argued that the second phase where only memory B cells are activated is more likely to be associated with antigen on follicular den

ISSN:0014-2980    

DOI:10.1002/eji.1830160609

出版商:WILEY‐VCH Verlag GmbH    

年代:1986

数据来源: WILEY

摘要:

AbstractThe expression on a significant number of thymocytes of idiotypic structures (Ti) restricted to HPB‐ALL or Jurkat cells is demonstrated. As many as 2‐4% of thymocytes were stained with anti‐Ti HPB‐ALL or anti‐Ti Jurkat monoclonal antibodies, when analyzed by flow microfluorometry. Immunohistochemical localization studies performed on frozen thymus specimens of either fetal or pediatric origin indicated a scattered distribution of Ti‐positive cells in both the cortex and the medulla. From lysates of125I‐labeled pediatric thymocytes, anti‐Ti HPB‐ALL and anti‐Ti Jurkat monoclonal antibodies precipitated disulfide‐linked heterodimers comparable to those precipitated from125I‐labeled HPB‐ALL or Jurkat cells as shown by sodium dodecyl sulfate‐polyacrylamide g

ISSN:0014-2980    

DOI:10.1002/eji.1830160610

出版商:WILEY‐VCH Verlag GmbH    

年代:1986

数据来源: WILEY

摘要:

AbstractA T3 complex‐bearing subpopulation was characterized within anin vivocycling T4−8−early thymocyte compartment which contains cells constitutively expressing interleukin 2 and transferrin receptors. We show differentiationin vitroof both mature subsets of thymocytes (T3+4+8−and T3+4−8+) from the above T4−8−compartment, their appearance being preceded by cells in a T3+4−8−intermediate stage. Furthermore, those mature thymocytes generatedin vitrocontain functionally competent cells which use T3, T4 and T8 structures for their cytolytic activity. The finding of T3+4−8−thymocytesin vivo, together with the observation that T3 antigen expression precedes that of T4 or T8 moleculesin vitro, shows that T3 (and presumably Ti) is present early in ontogeny, and suggests that T3+4−8−cells constitute an “intermediate” stage relevant to the connection between early precursors and mature thymocytes

ISSN:0014-2980    

DOI:10.1002/eji.1830160611

出版商:WILEY‐VCH Verlag GmbH    

年代:1986

数据来源: WILEY