摘要:

AbstractThe antigen‐mediated activation of a number of T cell clones by bone marrow (BM) cells cultivated in the presence of various colony‐stimulating factor (CSF) preparations was investigated. BM macrophages (BMMϕ,) grown in L929 cell supernatant as a crude source of macrophage colony‐stimulating factor (M‐CSF) as well as BM cells propagated in the presence of recombinant M‐CSF exhibited transient antigen presentation potential to some T cell clones, being maximal on day 7 and having declined to a low level by day 19 ofin vitroculture. Treatment of these long‐term‐cultivated BMMϕ, populations with recombinant interferon‐γ (IFN‐γ) resulted in predominant antigen presentation capacity. In contrast, BM cells differentiated in the presence of recombinant granulocyte (G)M‐CSF developed highly efficient accessory cell function to all T cell clones examined. This function became apparent earlier, was retained during the time period tested (up to day 19 of continuous culture) and did not require prior stimulation by IFN‐γ. The functionally competent cells were shown to belong to the monocyte/macrophage lineage. These findings are consistent with the demonstration of substantial levels of major histocompatibility complex (MHC) class II molecules synthesized by GM‐CSF‐cultured BM cells in the absence of exogenous IFN‐γ. In contrast, M‐CSF grown BM cells synthesized only minute amounts of Ia antigens unless they were stimulated by IFN‐γ. Because GM‐CSF‐cultivated BM cells proved clearly superior to M‐CSF‐grown and IFN‐γ‐activated BM cells with respect to antigen‐presenting capacity but exhibited lower levels of MHC class II molecules, other properties acting in addition to surface Ia antigens might be respo

ISSN:0014-2980    

DOI:10.1002/eji.1830180802

出版商:WILEY‐VCH Verlag GmbH    

年代:1988

数据来源: WILEY

摘要:

AbstractThe present study elucidates the mechanism whereby viral xenogenization of highly metastatic ESb lymphoid tumor cells increases tumor immunogenicity and syngeneic tumor‐specific T cell responses in comparison to nonmodified tumor cells. It was found that the frequency of cytotoxic T lymphocytes specific for the ESb tumor‐associated transplantation antigen (TATA) and the cytotoxic anti‐tumor activity in bulk cultures of immune spleen cells were significantly increased (by factor 3 and 25, respectively) when using virus‐modified tumor cells. An amplified response was observed bothin vivoandin vitrowhich might explain the demonstrated effectiveness of this approach for postoperative immunotherapy of ESb metastases.For the stimulation of tumor‐specific cytolytic T lymphocytes (CTL) the ESb tumor cells which are highly metastatic were infected with an avirulent strain of the paramyxovirus Newcastle Disease Virus (NDV). Infection of ESb cells with low amounts of NDV was sufficient to lead to an increase in cytolytic activity of tumor‐specific CTL after sensitizationin vivoand restimulationin vitro.In a sensitive limiting dilution mixed leukocyte‐tumor cell microculture system the direct effect of viral modification on the frequency and specificity of CTL was investigated. The number of ESb‐specific CTL per spleen could be raised from about 3300 (without modification) to 9100 by bothin vivoandin vitroapplication of ESb‐NDV. One appliction of ESb‐NDV (in vivoorin vitro) increased the number of CTL to 4900 and 4600, respectively. In split‐type experiments it could be shown at the clonal level that viral modification did not alter the specificity of ESb‐specific CTL. No CTL clones directed against viral antigens or new antigenic determinants were detected. The results indicate that in this system the effect of viral xenogenization is not due to recognition of additional xenoor neoantigens. NDV modification instead led to a selective augmentation of the TATA‐specific CTL response. In this respect it is remarkable since other methods to increase ESb tumor immunogenicity such as mutagenization or co‐expression of minor H antigens were shown before to activate additional CTL clones without affecting the

ISSN:0014-2980    

DOI:10.1002/eji.1830180803

出版商:WILEY‐VCH Verlag GmbH    

年代:1988

数据来源: WILEY

摘要:

AbstractWe have previously reported (Nature1982.299:361) that the transplacental transfer ofDipetalonema viteaemicrofilariae (mf) can induce an antigen‐specific tolerance in rats. Rats thus tolerized have serum factor(s) which block(s) antigen‐specific lymphocyte proliferation. The results of experiments involving fractionation of antisera from tolerant animals indicate that the inhibitory activity for antigen‐specific blastogenesis resides in IgG antibodies. Absorption of IgG (eluted from protein A) with specific filarial antigens reduced the inhibition from 58% to 9% whereas a similar immunosorption of IgG size fraction (obtained by applying to AcA 34 Ultrogel) resulted in a decrease from 72% to 35%. This suggests that IgG size fraction might include factor(s) derived from mf and was partially blocking the blastogenic response. Since the tolerant animals harbor only mf, we have used radiolabeled mf surface antigens for immunoprecipitation by antisera from tolerant animals. Antibodies from tolerant animals have a different specificity for filarial antigens compared to those from immunocompetent and mf‐resista

ISSN:0014-2980    

DOI:10.1002/eji.1830180804

出版商:WILEY‐VCH Verlag GmbH    

年代:1988

数据来源: WILEY

摘要:

AbstractHuman CD4  +T helper cells were separated into CD4+45R+and CD4+45R−cells. When stimulated with the polyclonal activator staphylococcal enterotoxin A in the presence of autologous monocytes, these two subsets exhibited a striking difference in production of interleukin 2 (IL2) and interferon‐gamma (IFN‐γ). While the CD4+45R_subset produced maximal amounts of IL2 within 24 h and IFN‐γ within 72 h, the CD4+45R+subset produced no IL2 within 24 h and merely marginal amounts of IFN‐γ as assayed after 24 to 96 h. This discrepancy between the subsets was found when the cells were stimulated by other accessory cell‐dependent activators and by the accessory‐independent combination of the calcium ionophore A23187 and the phorbol ester 12‐O‐tetradecanoylphorbol 13‐acetate as well. The inability of the CD4′+45R−cells to produce IL2 during the first day of culture was not due to any modulation of either the CD4+or the CD45R antigens, as purified CD4+45R−cells obtained by negative panning selection with the reciprocal UCHLl monoclonal antibody responded in a similar manner as the positively selected sorted CD4+45R−cells. Analysis of the kinetics of IL2 production by the two T helper cell subsets clearly demonstrated that the IL2 recorded after 1 day of culture was entirely produced by the CD4+45R−cells, whereas the CD4+45R−cells produced IL2 during and after the second day of culture. This discrepancy in kinetics was not due to an increased absorption of IL2 by the CD4+45R−cells during the first day of culture. In contrast, the rate of absorption of IL2 during the first and second day of culture and the expression of IL2 receptors were higher in the CD4+45R−than in the CD4+45R−cell cultures. Despite these findings the CD4+45R−cells consistently showed a stronger proliferative response than the other cell subset. Addition of recombinant IL 2 (rIL 2) did not render the CD4′45R′ cells capable of producing IFN‐γ, but small amounts of RIL2 enhanced their proliferative response more efficiently than that of the CD4+45R−cells. Addition of anti‐Tac resulted in a reduction of IFN‐y production and of DNA synthesis by the CD4+45R−cells. Similarly the DNA synthesis and the small amounts of IFNγ

ISSN:0014-2980    

DOI:10.1002/eji.1830180805

出版商:WILEY‐VCH Verlag GmbH    

年代:1988

数据来源: WILEY

摘要:

AbstractWe have used a monoclonal antibody (mAb)‐specific for murine T suppressor (Ts) cells (mAb 14‐12) to study the role of T cells in tolerance and immunoregulation. We demonstrate that mAb 14‐12 can blockin vivoT, cell activity in a variety of experimental systems. It prevents the induction of Ts cells induced by i.v. injection of the water‐soluble hapten 2,4,6‐trinitrobenzene sulfonic acid, and the protein antigen bovine serum albumin. When 14‐12 mAb is given prior to the i.v. injection of Tstrinitro phenyl‐conjugated spleen cells (TNP‐SC) it blocks the induction of T, cells and sufficiently overcomes suppression so that TNP‐SC is able to induce immunity. mAb 14‐12 can convert nonresponder mice into responders for the Ir gene‐controlled response to the random terpolymer L‐glutamic acid60‐L‐alanine30‐L‐tyrosine10(GAT), and can substitute for cyclophosphamide in overcoming a suppressor barrier in the adoptive transfer of contact sensitivity. Administration of 14‐12 mAb just prior to immunization results in the augmentation of contact sensitivity, antibody and plaque‐forming cell responses. These results demonstrate the versatility of this reagen

ISSN:0014-2980    

DOI:10.1002/eji.1830180806

出版商:WILEY‐VCH Verlag GmbH    

年代:1988

数据来源: WILEY

摘要:

AbstractPreviously, we have shown that paraformaldehyde‐fixed monocytes are able to fully complement, in terms of [3H]dThd incorporation, a primary stimulus delivered to purified T cells by monoclonal antibodies (mAb) reacting with CD3 or CD2 molecules. Here, we show that depending on the stimulus used (CD3 mAb or different pairs of CD2 mAb) HLA class I molecules from monocytes are directly involved in complementary signals provided to T cells. This was evidenced by the following observations: (a) mAb reacting with the heavy or light chain of class I molecules, or their Fab fragments, completely blocked proliferation of peripheral blood lymphocytes (PBL) activated by CD3 mAb; (b) mAb against the heavy chain of HLA class I but not against p2‐microglobulin partially blocked (= 50%) PBL activation by the CD2 "GT2 + T1l1" mAb pair but did not block activation by CD2 "D66 + T111" mAb; (c) this pattern of inhibition was observed when anti‐class I mAb were used in the soluble phase or when they were bound to monocytes subsequently fixed with paraformaldehyde and cultivated with purified autologous T cells; (d) fixed monocytes are able to restore interleukin (IL) 2 receptor expression on purified T cells stimulated by CD3 mAb or CD2 "GT2 + T111contrary to anti‐HLA class I mAb‐pretreated monocytes. The inhibitory effects of anti‐HLA class I mAb bound to monocytes were not found to be reversed by recombinant IL2 or recombinant IL1. We assume that HLA class I would be involved in two or more signals delivered to T cells by monocytes, the requirement in those signals depending on the initial stimulus applied to T cells. Transmission of one signal would require a conformation of the HLA molecule inhibitable by both or either anti‐heavy and anti‐light chain mAb. In searching for the counterpart to the accessory cell HLA class I molecule, we found that both CD4+and CD8+cells responded to stimulation via CD2 or CD3 mAb. However, within the CD4 subsets, the CD4+w29−subset did not respond while the reciprocal subset did. This was not due to a lack of IL2, as shown by adding rIL2. Since the CD4+w29−subset is committed to the induction of suppression while the reciprocal subset to the induction of help, one can forsee how the immune response could develop in one direction or the other depending on the type of interaction that occurs durin

ISSN:0014-2980    

DOI:10.1002/eji.1830180807

出版商:WILEY‐VCH Verlag GmbH    

年代:1988

数据来源: WILEY

摘要:

AbstractCurrent data suggest that some astrocytes, one of the 3 main types of macroglia in the central nervous system (CNS), can be induced by interferon‐y (IFN‐γ) to express major histocompatibility complex class I1 antigens (immune‐associated or Ia) and present antigen to T lymphocytes. In contrast, oligodendrocytes, another type of macroglia, cannot be induced to express Ia. The astrocytes which have been shown to express Ia are from a particular glial lineage and are called type‐1 astrocytes. The oligodendrocyte‐type‐2 astrocyte (0‐2A) lineage, which gives rise to oligodendrocytes, also gives rise to a second class of astrocytes called type‐2 astrocytes and the ability of type‐2 astrocytes or the common O‐2A progenitor cell to express Ia is not known. We have now found that both type‐2 astrocytes and O‐2A progenitor cells can be induced to express Ia by IFN‐Γbut Ia expression is not induced in oligodendrocytes in parallel cultures. Thus, it appears that differentiation of O‐2A progenitor cells into oligodendrocytes is specifically associated with a loss of inducibility of Ia. This apparent loss of the capacity for Ia expression, and presumably antigen presentation, in oligodendrocytes (the cells which produce myelin in the CNS) is of particular interest in view of the ability of immunization of myelin components to produce autoimmu

ISSN:0014-2980    

DOI:10.1002/eji.1830180808

出版商:WILEY‐VCH Verlag GmbH    

年代:1988

数据来源: WILEY

摘要:

AbstractAlthough many studies have attempted to elucidate how cytotoxic T (Tc) lymphocytes cause the death of target cells, the mechanism is still controversial. In the present study the effect on the integrity of the lysosomes of the target cell has been investigated. We show here that the specific recognition and attachment of cloned type A influenza‐specific Tccells to A/X31 influenza virus‐infected target cells caused rapid change in the amount of lysosomal naphthylamidase activity that was bound within the lysosomes, indicating that the lysosomal membianes in the target cells had been totally labilized. Target cells infected with type B influenza virus served as controls. We therefore suggest that the viral specificity of Tc, lymphocytes allows for recognition and intimate membrane contact with suitably infected targets. This intimate contact induces sufficient perturbation of the target cell plasma membrane so as to cause total labilization of the target cell lysosomes which could account for intracellular ly

ISSN:0014-2980    

DOI:10.1002/eji.1830180809

出版商:WILEY‐VCH Verlag GmbH    

年代:1988

数据来源: WILEY

摘要:

AbstractNonresponder SJL mice produce low levels of antigen‐specific IgE after immunization, compared to responder strains. Young athymic BALB/c nude mice are unable to produce antigen‐specific or total IgE in their serum. These mice also have very low numbers of background IgE‐secreting cells in their lymphoid organs. High‐responder BALB/c mice do have substantial numbers of background IgE‐secreting cells while low‐responder AKR mice show intermediate numbers. Similar differences were found when analyzing lipopolysaccharide (LPS)‐reactive B cells in cell suspensions of spleen and bone marrow in limiting dilution cultures. Limiting dilution analysis of T cell‐depleted splenic B cell cultures revealed that the defective IgE production in SJL mice is not due to an intrinsic B cell defect. This defect can be substantially overcome by addition of exogenous interleukin 4 (IL4) to these cultures. Furthermore, it was shown in limiting dilution cultures that SJL thymocyte feeder cells were able to suppress IgE production by LPS‐activated high‐responder BALB/c B cells. The addition of IL4 or neutralizing antibodies against IL4 or interferon‐y to these cultures helped to overcome this suppressive effect to a large extent. We conclude that different IgE responder types are caused, at least in part, by a defective IL4 production or by a defect in the TH2 system that is functionally detectable at th

ISSN:0014-2980    

DOI:10.1002/eji.1830180810

出版商:WILEY‐VCH Verlag GmbH    

年代:1988

数据来源: WILEY

摘要:

AbstractHuman serum IgG subclasses have been measured by a sensitive enzyme‐linked immunoassay in 52 subjects with severe genetic deficiency of a complement component. The mean serum IgG4in 4 subjects with C3 deficiency was 8.2 γg/ml and in 14 subjects with (C1‐4 deficiency was 27.9 γg/ml. These means are severely depressed compared with the mean normal IgG4 of 292 γg/ml. IgG4 levels in C5‐9 deficiency (175 γg/ml) and ClINH deficiency (179 γg/ml) did not differ significantly from normal. Serum IgG2was reduced significantly, but far less severely than IgG4, in C3 and in some cases of C1‐4 deficiency. IgGland IgG3levels were within the normal range in all complement‐deficient groups. Age differences between the groups do not explain the very low levels of IgG4 in C1‐4 and C3 deficiency. These data suggest that serum IgG4 synthesis is dependent on an intact classical, but not alternative, pathway for activation of C3 and that IgGCcommitted B cells require a complement‐dependent maturation pathway not required by B cells committed to other IgG isotypes. IgG4antibody responses are associated with secondary responses to T‐dependent antigens. The possibility that IgG4may be the product of a memory B cell which has been through a stage of differentiation in a germinal

ISSN:0014-2980    

DOI:10.1002/eji.1830180811

出版商:WILEY‐VCH Verlag GmbH    

年代:1988

数据来源: WILEY