摘要:

AbstractThe role of interleukin 2 (IL 2) in the induction of human B cell differentiationin vitrowas studied. IL2 was unable to induce immunoglobulin (Ig) production in non‐T cells either in the presence or absence of pokeweed mitogen (PWM). However, IL2 alone could induce Ig production in non‐T cells when irradiated T cells were present. Similar to the PWM‐driven system helper activity was delivered by T4+but not T8+cells. Apparently, IL2 acts on T4+cells and induces these cells to deliver the actual helper signal(s) for Ig production by B cells. Whereas in the PWM‐driven system only T8+cells suppress Ig synthesis, ILZdriven Ig synthesis was suppressed by both T4+and T8+cells added to a mixture of non‐T cells and irradiated T4+cells. This suppressor activity could be abrogated by irradiation. PWM was shown to induce IL2 production in both T4+and T8+cells. Moreover, PWM‐induced Ig synthesis, like IL2‐induced Ig synthesis, could be totally abrogated by a monoclonal antibody against the human IL2 receptor (anti‐Tac). These findings, coupled to the innate Ig‐inducing capacity of IL 2, indicate a role for IL 2 in the PWM‐driven system. The mechanism of suppression in both the PWM‐ and the IL 2‐driven systems was not shortage of IL 2 in the culture due to consumption or inhibition of production of IL 2. Moreover, the T8+cells produced IL2, despite their failure to help Ig synthesis. Helper T cell activity can thus be divided into two distinct activities: (a) IL2 production and (b) the ability to deliver the actual helper signal such as helper factors for B cell differentiation. This insight allows a better evaluation of the immunoregulatory activities of T cell subset

ISSN:0014-2980    

DOI:10.1002/eji.1830150202

出版商:WILEY‐VCH Verlag GmbH    

年代:1985

数据来源: WILEY

摘要:

AbstractNZB mice, DBA/2 mice and reciprocal F1hybrids between both strains were studied from birth to two months of age for the secretion of a serum thymic factor, thymulin (formerly named Facteur Thymique Sérique) and for spontaneous and antigen‐induced immune responses: spontaneous splenic anti‐2,4,6‐trinitrophenyl (TNP) plaque‐forming cells (PFC), spontaneous IgM serum levels, immune direct anti‐sheep red blood cells (SRBC) PFC and immune serum antibody production to human gamma globulin (HGG) as well as susceptibility to tolerance induction by deaggregated HGG. An early decline of thymulin serum level was detected from two weeks of age both in NZB mice and F1hybrids, the latter maintaining a level intermediate between that of both parental strains. Such a fall of circulating thymulin was associated to a decreased number of thymulin‐secreting cells.F1hybrids and NZB mice exhibited at two and three weeks of age spontaneous anti‐TNP PFC in the spleen, and increased IgM serum levels as compared to DBA/2 mice. When immunized at birth with SRBC or at two weeks of age with HGG, NZB mice and F1 mice similarly exhibited a higher anti‐SRBC antibody response, as measured 5 days later by PFC numbers, and a higher anti‐HGG serum antibody production 2 weeks post‐immunization, than age‐matched DBA/2 mice. F1hybrids tended to develop with age spontaneous and immune antibody responses lower than NZB mice but still much higher than DBA/2 mice. Conversely, after tolerization at birth with deaggregated HGG NZB mice but not the F1hybrids produced higher titers of anti‐HGG antibodies upon challenge than similarly tolerized DBA/2 mice. DBA/2 mothered and NZB mothered Flhybrids did not differ for any parameter tested and no influence of t

ISSN:0014-2980    

DOI:10.1002/eji.1830150203

出版商:WILEY‐VCH Verlag GmbH    

年代:1985

数据来源: WILEY

摘要:

AbstractRecombinant interferon‐γ (IFN‐γ) induced the expression of HLA‐DR when added to the culture medium of HLA‐DR−melanoma cell lines. In addition, IFN‐γ induced the expression of another class II antigen, HLA‐DC, on a HLA‐DR+and ‐DC−melanoma cell line and to a lower level on a ‐DR and ‐DC−melanoma line. IFN‐γ also enhanced the expression of HLA‐ABC and β2‐microglobulin, as well as HLA‐DR on DR+melanoma cells. In contrast, IFN‐α gave no induction of expression of HLA‐DR and DC on two DR−melanoma lines, while it did enhance the expression of HLA‐ABC and of β2‐microglobulin. The expression of 3 out of 6 melanoma‐associated differentiation antigens was enhanced by IFN‐γ treatment. The modulation of antigens by IFN‐γ was both dose and time dependent. A minimum incubation time of 48 h was necessary for the appearance of HLA‐DR on the two HLA‐DR−melanoma lines, whereas HLA‐ABC and β2‐microglobulin were already increased after 24 h. A dose of 20 U/ml IFN‐γ started to induce the expression of HLA‐DR and DC on melanoma cells GLL‐19 and Me‐43 and a plateau of maximum antigen expression was reached with 100 U/ml. Analyses of IFN‐γ‐treated cells by flow micro‐fluorometry showed a homogeneous distribution of increased staining intensity rather than the appearance of two cell populations. Immunoprecipitation experiments using detergent‐solubilized125I‐labeled membrane proteins of IFN‐γ‐treated melanoma cells and a monoclonal anti‐HLA‐DR antibody confirmed the presence of HLA‐DR antigens. When IFN‐γ‐treated cells were cultured without IFN the induced or enhanced expression of HLA antigens was reversible. Eight days after removal of IFN, the HLA‐DR level was reduced by more than 90% and the level of HLA‐ABC and β2‐microglobulin by more than 50%. The demonstration of the ability of HLA‐DR−melanoma cells to express HLA‐DR after IFN‐γ treatme

ISSN:0014-2980    

DOI:10.1002/eji.1830150204

出版商:WILEY‐VCH Verlag GmbH    

年代:1985

数据来源: WILEY

摘要:

AbstractPrevious work has shown that the primary IgM plaque‐forming cell response of inbred mice to xenogeneic red blood cells (RBC) including sheep, horse and chicken RBC is under the control of two polymorphic genes or sets of genes, one linked to the Igh linkage group and the other of unknown linkage but unlinked to H‐2 and a variety of other known genetic markers. Both genes together control B cell function but do not influence the function of T cells and macrophages. Thus, this system permits the study of two polymorphic loci that control B cell responsiveness. In this study we analyze the role of the Igh region in further detail. In bulk cultures and limiting dilution experiments, we confirm its exclusive influence on B cells also when analyzed separately from the background gene,i.e.in Igh‐congenic strains. Moreover, we find in the majority of experiments 4‐5‐fold differences in sheep RBC‐specific B cell precursor frequencies among lipopolysaccharide‐reactive cells from 3 pairs of Igh‐congenic high and low‐responder strains. Similar frequency differences exist for horse RBC and chicken RBC‐specific B cells but not for B cells with specificity for (4‐hydroxy‐5‐iodo‐3‐nitrophenyl)acetyl (NIP)‐gelatine. These differences are independent of the frequencies of B cells responding to lipopolysaccharide which are shown to be equal between Igh‐congenic pairs of strains. Since the differences in RBC‐specific B cell frequencies closely resemble the differences in bulk culture responses to the corresponding RBC, we conclude that the role of the Igh linkage group in controlling responsiveness to RBC lies in a selective influence on the B cell repertoire concerning precursor cells for RBC specificity. In addition, we find that the VHpart of Igh is responsible for the observed frequency differences, suggesting that VHgerm‐line genes directly influence the compos

ISSN:0014-2980    

DOI:10.1002/eji.1830150205

出版商:WILEY‐VCH Verlag GmbH    

年代:1985

数据来源: WILEY

摘要:

AbstractSeventeen monoclonal antibodies specific for IgM and one ϰ light chain‐specific antibody were used to test the effect of immunoglobulin (1g)‐specific antibodies on B cell activation. In soluble form, either alone or together with T cell‐derived growth and maturation factors, none of the antibodies stimulated resting B cells to divide or secrete Ig. The soluble antibodies inhibited lipopolysaccharide‐induced B cell activation. The inhibitory effect of the antibodies was independent of their Fc part. When immobilized, the same antibodies could activate B cells to proliferate and together with T cell‐derived maturation factors to mature to plasma cells. Occupation by immobilized antibody of determinants on any of the four constant region domains and on the light chain of surface Ig can lead to the stimulation

ISSN:0014-2980    

DOI:10.1002/eji.1830150206

出版商:WILEY‐VCH Verlag GmbH    

年代:1985

数据来源: WILEY

摘要:

AbstractSuppression of the mixed lymphocyte reaction (MLR) exerted by splenocytes derived from mice treated with fractionated total lymphoid irradiation (TLI, 200 rds × 8) was analyzed by various criteria in order to characterize the phenotype of the cell type(s) responsible for suppression. TLI‐induced suppressor cells could not be eliminated by removal of cells bearing surface immunoglobulin, Thy‐1, Lyt‐2 and TL, and thus could not be ascribed to lymphocytes of the B or T cell lineage. Suppressor cells were large, and nonadherent to nylon wool, Sephadex G‐10 and plastic surfaces. Suppressor activity of TLI splenocytes was predominantly located in fractions of cells bearing receptors for soybean agglutinin (SBA), peanut agglutinin (PNA) or both lectins. SBA+, PNA+′, sequentially agglutinated (SBA followed by PNA) SBA+PNA+and (PNA followed by SBA) PNA+SBA+suppressor cells were radioresistant upon exposure to 1000 rdsin vitro.Cells bearing the receptor for PNA but lacking that for SBA (PNA+SBA−) had sharply reduced suppressor activity. However, a radiosensitive PNA−suppressor cell subset was also documented in the spleen of TLI‐treated mice. Thus, suppressor cells could best be physically separated from nonsuppressors by the SBA lectin. SBA+suppressor cells were found, by scatter analysis, to include the population of large cells characteristic of TLI splenocytes, whereas SBA−cells were much smaller and almost exclusively devoid of suppressive capacity. The PNA receptor was found to further dissect the SBA+suppressor cells into two distinct subpopu‐lations: radioresistant SBA+PNA+cells and radiosensitive SBA+PNA−cells. In summary, we suggest here the presence of at least two suppressive populations induced by TLI: (a) radioresistant SBA+, PNA+, SBA+PNA+or PNA+SBA+cells, and (b) radiosensitive PNA−and SBA+PNA−cells. Similar subsets of MLR suppressor cells can be isolated from normal bone marrow cells and splenocytes of nude mice, suggesting that suppression is mediated by large, immature, nonlymphoid cells which might migrate from shielded bone marrow compartments into the

ISSN:0014-2980    

DOI:10.1002/eji.1830150207

出版商:WILEY‐VCH Verlag GmbH    

年代:1985

数据来源: WILEY

摘要:

AbstractIn this study we have determined the frequency and distribution of interleukin 2 (IL2)‐producing cells and their precursors (IL2‐P) in the two major subsets of human T cells. The two subsets were identified on the basis of their reactivity (or lack thereof) with anti‐T4 or anti‐T8 monoclonal antibodies. T4+T8−and T4−T8+cells were first isolated from peripheral blood T cell populations by positive or negative selection using the fluorescence‐activated cell sorter, and then analyzed for total IL2‐P and cytolytic T lymphocyte precursor (CTL‐P) frequencies using a limiting dilution microculture system which allows clonal growth of every T cell. The results indicated that 50‐60% of peripheral blood T cells consisted of IL2‐P. In the T4+T8−subset (which represents 60‐65% of all T cells) about 75% of the cells were IL2‐P, whereas about 15% of T4−T8+cells exhibited this functional potential. In contrast, about 3% and>95% of T4+T8−and T4‐T8+cells, respectively, were CTL‐P. Thus, these data provide direct evidence that there is no absolute correlation between the surface phenotype and the functional potential of human peripheral blood T cells. Moreover, it is evident from this frequency analysis that a significant proportion of T4−T8+cells have a dual functional potential. IL2‐P and CTL‐P frequencies were also determined in T cell populations which had been activated in allogeneic mixed lymphocyte culture. The IL2‐P frequencies in total T, T4+T8−and T4−T8+MLC populations were 30, 45 and lo%, respectively. Comparative analysis of IL 2 production and CTL activity at the clonal level confirmed that up to 20% of alloreactive CTL with the T4−T8+surface phenotype were able to produce IL2 upon specific stimulation. This dual func

ISSN:0014-2980    

DOI:10.1002/eji.1830150208

出版商:WILEY‐VCH Verlag GmbH    

年代:1985

数据来源: WILEY

摘要:

AbstractIntroduction of a reactive monohaptenic chemical into the sensitized organism will not normally result in elicitation of immediate reactions. Rather, the first products of chemical conjugation to suitable carriersin vivoare monohaptenic conjugates which are inhibitory according to the bridging concept, stating that the initiating event for mast cell and basophil activation is a cross‐linking of membrane‐bound antibody by dihaptenic or oligohaptenic antigen. Simple calculations and quantitative data are presented to show that built‐in inhibition is indeed a powerful barrier to any rapidly occurring allergenic manifestation which depends on the formation of divalent conjugates. If and when such a reaction does nevertheless occur, special requirements have to be invoked. One possibility is that the chemical or drug as such,i.e.without conjugation to a carrier, is an elicitor of anaphylaxis. Such compounds are known in a guinea pig passive cutaneous anaphylaxis model system, but there is evidence that they may also play a role in clinical situations. These monovalent elicitors possess in addition to the haptenic moiety an auxiliary group. The auxiliary group requirements were studied in the guinea pig passive cutaneous anaphylaxis system by using synthetic peptides with an N‐terminal 2‐carboxy‐4,6‐dinitrophenyl group as the hapten and phenylalanine and modified phenylalanine at the C‐terminus as auxiliary group. The conclusions are that effective auxiliary function depends on the benzene ring and neighboring carboxyl groups in selected positions. Anaphylactogenicity is high when the haptenic and auxiliary groups can act independently,i.e.when separated by a peptide chain of considerable length. Potent anaphylactogens with close linkage of the two groups have, however, also been found. It is unlikely that the passive cutaneous anaphylaxis elicitations observed here are mediated by some form of indirect bridging of membrane

ISSN:0014-2980    

DOI:10.1002/eji.1830150209

出版商:WILEY‐VCH Verlag GmbH    

年代:1985

数据来源: WILEY

摘要:

AbstractAlloproliferative primed lymphocyte typing (PLT) clones recognizing determinants associated with HLA‐DR/Dw, SB, MB, or novel “SB‐like” gene products were screened for their ability to suppress lymphoproliferative responses in primary and secondary mixed lymphocyte cultures (MLC), and for their surface marker pheno‐types. Two nonsuppressive HLA‐D specific PLT clones were OKT4−, OKT+whereas all others possessed an OKT4+, OKT8−, Leu‐8−phenotype. All clones secreted interleukin 2 (IL2) after specific stimulation. The eight PLT clones specific for “SB‐like” antigens strongly suppressed MLC, whereas only one of 35 DR/Dw‐specific, and none of 20 SB‐specific PLT clones did so. Suppressive activity of such PLT clones was not restricted by major histocompatibility complex products, was radioresistant (20 Gy), and was not caused by absorption of IL2 or by cytotoxicity of the cloned cells. Suppressive clones exerted their effects directly on proliferating T cells, as assessed by their ability to prevent growth of cloned PLT cells stimulated by B cell lines, and their ability to block primary MLC even when added 96 h after the start of the 144‐h culture. Culture supernatants from suppressive, but not from nonsuppressive, PLT clones also strongly and nonspecifically inhibited lymphoproliferative responses. The suppressive factor(s) was not dialyzable, not sensitive to pH 2 or heat treatment and not cytotoxic. Thus, all T cell clones proliferating against novel “SB‐like” but not SB antigens, as well as rare clones specific for D region determinants, possess powerful nonspecific suppressive activities dissociated from their “helper‐related” OK

ISSN:0014-2980    

DOI:10.1002/eji.1830150210

出版商:WILEY‐VCH Verlag GmbH    

年代:1985

数据来源: WILEY

摘要:

AbstractThe molecular forms and antigenic heterogeneity of the leukocyte‐common antigen (L‐CA) of rat lymphocytes have been analyzed. Thymocytes show one main band at 180 kDa, T cells four bands at 180,190, 200 and 220 kDa and B cells one broadband at about 240 kDa. T helper and T cytotoxic cell subsets show the same four bands with some differences in the proportion of each.Four mouse monoclonal antibodies (MRC OX‐1, 28, 29 and 30) reacted with all molecular forms of L‐CA and fell into two sets that were noncompetitive in binding to L‐CA (MRC OX‐1, 28, 29 vs. OX‐30). The antigenic determinants seen by all these antibodies were lost when L‐CA was reduced and alkylated. Three antibodies (MRC OX‐22, 31 and 32) reacted selectively with B cells, T cytotoxic cells and about 2/3 of T helper cells. OX‐22 and OX‐31 competed for binding but were noncompetitive with OX‐32. All these antibodies bound to a subfraction of the 190, 200 and 220‐kDa forms of T cell L‐CA but not at all to the 180‐kDa form of T cells or thymocytes. One antibody bound to B cells only (MRC OX‐33) and precipitated a subfraction of B cell L‐CA. With all the antibodies that did not label thymocytes the antigenic determinants survived reduction and alkylation. Subsequent proteolysis with trypsin then destroyed all determinants except the one reacting with MRC OX‐22 antibody, In this case tryptic peptides retained full antigenic activity which was, however, destroyed

ISSN:0014-2980    

DOI:10.1002/eji.1830150211

出版商:WILEY‐VCH Verlag GmbH    

年代:1985

数据来源: WILEY