摘要:

AbstractThe Lyt phenotype of T cells at different stages of response to mutant H‐2K antigens was determined by immunofluorescence using monoclonal rat anti‐Lyt antibodies. Previous observations indicated a differential expression of the two allelic forms of Lyt‐1 antigen on these cells. Since the rat antibodies recognize nonpolymorphic framework determinants of Lyt antigens, in our approach the expression of both Lyt‐1 alleles was analyzed with the same antibody. It was found that cells reacting to three different H‐2K mutants have the Lyt‐1,2 phenotype, regardless of the Lyt‐1 allele carried by the responder strain. The Lyt phenotype of responder cells remained unchanged after primingin vivo. However, cells recovered from cultures after secondary stimulationin vitrowere mainly Lyt‐2, with few Lyt‐1,2 and virtually no Lyt‐1 cells present. This change of Lyt phenotype ran in parallel with the loss of proliferative capacity to the priming antigen, but cytolytic activity of the cells remained unimpaired. Long‐term proliferation of T cells induced against mutant H‐2K antigens could only be maintained in the presence of a T cell growth factor. Cultures with growth factor contained almost exclusively Lyt‐2 cells and exerted strong cytolytic activity. These results demonstrate that the Lyt differentiation pathway of anti‐mutant T cells is from Lyt‐1,2 to Lyt‐2. Furthermore, the data suggest that no helper cells are induced in response to mutant H‐2K antigens. A model which incorporates these findings into current concepts of T

ISSN:0014-2980    

DOI:10.1002/eji.1830110302

出版商:WILEY‐VCH Verlag GmbH    

年代:1981

数据来源: WILEY

摘要:

AbstractHelper cells, with specificity for the haptens (4‐hydroxy‐3‐nitro‐phenyl)acetyl (NP) or (4‐hydroxy‐5‐iodo‐3‐nitro‐phenyl)acetyl (NIP), were raised in B10.BR mice byin vivopriming andin vitrolong‐term enrichment with hapten‐derivatized syngeneic spleen cells. Upon co‐culture with the homologous antigen (NP or NIP self), selected helper cells specifically responded by proliferation and by inducing large numbers of B cells to clonal expansion and immunoglobulin secretion. Criss‐cross experiments demonstrated the nonheteroclitic nature of antigen recognition by helper cells, as the proliferative and helper cell activites were in every case one order of magnitude higher when confronted with the homologous h

ISSN:0014-2980    

DOI:10.1002/eji.1830110303

出版商:WILEY‐VCH Verlag GmbH    

年代:1981

数据来源: WILEY

摘要:

AbstractThe relationship between surface antigen expression and function in the long‐term allospecific T cell line C.C3.11.75 was examined by flow microfluorometry, antiserum plus complement depletion and cell sorting. T cells of the line expressed Lyt‐1, but little or no Lyt‐2 antigens. Proliferation to cells bearing Iakdeterminants, generation of T cell‐replacing nonspecific helper factor in response to Iak‐positive cells and the killing of Iak‐positive targets were dependent only on Ly‐1 cells. No obvious heterogeneity was found in this cell line despite its disparate functional activities. The fact that Lyt‐2 molecules need not be present for killing directed against Ia determinants indicates that such molecules are not obligatory for the induction or delivery of killing and raises the question of what the role of Lyt molecules in T cell recognition or fu

ISSN:0014-2980    

DOI:10.1002/eji.1830110304

出版商:WILEY‐VCH Verlag GmbH    

年代:1981

数据来源: WILEY

摘要:

AbstractA range of monosaccharides were tested for their ability to inhibit a variety ofin vitroimmune responses. The most striking specific inhibition was produced by N‐acetyl‐D‐galactosamine (GalNAc). This sugar strongly inhibited the secondary IgG antibody response to two different hapten‐carrier systems, but had no effect on primary and secondary IgM responses, generation of cytotoxic T cells to alloantigens and mixed lymphocyte reactions. By exposing secondary antibody cultures to GalNAc for varying periods of time, it was observed that GalNAc only exerted its inhibitory effect on day 4 of the culture, the day when IgG plaque‐forming cells first appeared. Furthermore, GalNAc could override the action of T helper factor in T cell‐depleted cultures. Collectively, these data indicate that GalNAc inhibits the initiation of IgG synthesis probably by blocking the interaction of a helper factor for IgG synthesis with its

ISSN:0014-2980    

DOI:10.1002/eji.1830110305

出版商:WILEY‐VCH Verlag GmbH    

年代:1981

数据来源: WILEY

摘要:

AbstractThe effects of anti‐receptor (anti‐idiotypic) immunity on autoimmune responses have been investigated in Buffalo (BUF) rats with autoimmune thyroiditis. As compared to other animal models of autoimmune desease, BUF rat thyroiditis has the following advantages: it occurs in an inbred strain, arises spontaneously (i.e.without the experimental administration of autoantigens and adjuvants) and is characterized by the production of autoantibodies to only one autoantigen, thyroglobulin. Finally, its pathogenesis is mediated by autoantibodies to rat thyroglobulin, and therefore this model is particularly suitable to study the effects of anti‐idiotypic reactions on those autoimmune disorders whose damage is caused by humoral immunity.The experiments reported in the present study show that first, heterologous anti‐idiotypic antibodies to autoantibodies against rat thyroglobulin have been produced and characterized. It has then been demonstrated that such anti‐idiotypic antibodies are capable of inhibiting thein vitrobinding between thyroglobulin and thyroglobulin autoantibodies obtained from BUF rats. It has also been shown that repeated injections of anti‐idiotypic antibodies into sublethally X‐irradiated BUF rats with autoimmune thyroiditis were followed by a significant change in the levels of circulating autoantibodies to rat thyroglobulin. These results provide evidence that in spite of the complexity of autoantigens and the heterogeneity of autoimmune responses, established autoimmune diseases may be controlled by sequential immunosuppression and anti‐idi

ISSN:0014-2980    

DOI:10.1002/eji.1830110306

出版商:WILEY‐VCH Verlag GmbH    

年代:1981

数据来源: WILEY

摘要:

AbstractThe isolation and propagation of functional antigen‐specific lines of T lymphoblasts is described. These lines were found to recognize foreign or self antigens in association with accessory cells of syngeneic major histocompatibility complex genotype. Intravenous inoculation of a T cell reactive only against myelin basic protein led to development of clinical paralysis in syngeneic rats. Thus, it is possible to study biological function as well as antigen specificity using T cell line

ISSN:0014-2980    

DOI:10.1002/eji.1830110307

出版商:WILEY‐VCH Verlag GmbH    

年代:1981

数据来源: WILEY

摘要:

AbstractFluorochrome‐conjugated antibodies specific for Cμ determinants and VHaallotypes were used to examine pre‐B cells and B lymphocytes for expression of these markers. The majority of μ+bone marrow pre‐B cells were shown to expressaallotypic determinants in conjunction with Cμ. Both pre‐B and B cells froma2a3heterozygous rabbits showed allelic exclusion of these allotypes. Pre‐B cells expressing the a2 or a3 specificities appeared to be generated in approximately equal numbers in heterozygotes, while B lymphocytes expressing a3 appeared to undergo preferential clonal expansion very early in development. It was also observed that rabbit bone marrow and blood contained a population of myeloid cells which, ina2a3heterozygotes, stained for both a2 and a3 determinants. The frequencies of this cell type, which exhibited bright immunofluorescence staining foraallotypes, could not be reduced by prolonged incubation at 37°C but were readily reduced after cell suspensions were treated with low pH buffer. It is concluded that these myeloid cells bear high avidity Fc receptors for serum immunoglobulin and may be the culprits in studies which have found production of twoaorballotypes by individual

ISSN:0014-2980    

DOI:10.1002/eji.1830110308

出版商:WILEY‐VCH Verlag GmbH    

年代:1981

数据来源: WILEY

摘要:

AbstractSpecific antibody responses to influenza virus were obtainedin vitrofrom human blood mononuclear cells (PBM). The response was T cell‐dependent, as shown by separation of PBM into E rosette‐positive (E+) and ‐negative (E−) populations. The histocompatibility requirements for T‐B cell interactions in this response were analyzed by recombining E−and E+fractions from donors with varying degrees of HLA compatibility. No antibody formation was obtained from any allogeneic combination except for the special case of HLA identical siblings. As these experiments included combinations with shared or identical HLA‐DR specificities, it was unlikely that genetic restriction alone could account for the failure of T‐B cell collaboration. Evidence that suppression was responsible for the lack of antibody formation was obtained from experiments in which allogeneic E+cells profoundly depressed specific antibody responses of intact PBM. In contrast, no such suppression was seen in pokeweed mitogen‐driven polyclonal Ig synthesis for which there are no major histocompatibility complex requirements for T cell help. The suppressor activity of allogeneic E+cells was found to be radiation‐sensitive. By irradiating E+cells, it was, therefore, possible to test for T cell help across an HLA barrier without unwanted suppressor effects. Under these conditions, (irradiated) E+cells were able to collaborate with allogeneic E−cells even with no HLA alleles in common. This was true even when autologous monocytes were depleted from the helper E+population. Supernatants collected from antigen‐driven cultures of allogeneic E−and E+cells were able to replace helper T cells in the specific antibody response to influenza virus. The apparent lack of genetic restriction in these responses might, therefore, be explained by the production of a no

ISSN:0014-2980    

DOI:10.1002/eji.1830110309

出版商:WILEY‐VCH Verlag GmbH    

年代:1981

数据来源: WILEY

摘要:

AbstractDinitrophenylated (DNP) conjugates of Ficoll, hydroxyethyl starch, levan, dextran, type 3 pneumococcal capsular polysaccharide SIII, pectin, alginic and hyaluronic acid at various epitope densities were tested for their capacity to inhibit secondary IgG anti‐DNP antibody responses using anin vivotransfer system. Some aminobenzylarsonate conjugates were examined similarly. Conjugates of the acidic polysaccharides were markedly more effective than those of uncharged polysaccharides. Conjugates with high epitope densities were particularly tolerogenic. DNP conjugates of Ficoll and hydroxyethyl starch elicited prolonged IgM responses over a wide dose range, and there are indications in the literature that conjugates of dextran do likewise. All the polysaccharide conjugates, labeled with radioiodine, persisted in the body for long periods (half‐lives 8.5–63 days), and all were cleared rapidly from, but remained detectable in the blood for many days. Gross tissue distributions varied markedly from one conjugate to another, and autoradiography revealed unexpected differences in cellular localization. Despite substantial retention in the liver, some uncharged polysaccharides were localized only in parenchymal and not in Kupffer cells. In the spleen, only the acidic polysaccharides were predominantly localized in red pulp macrophages, and the neutral polysaccharides were detectable exclusively, and in the case of Ficoll, hydroxyethyl starch and some dextrans very intensely in macrophages of the marginal zone of the white pulp. It is suggested that retention of thymus‐independent antigens in marginal‐zone macrophages favors, whereas trapping in red‐pulp macrophages diminishes immunogenicity, and that tolerogenic effectiveness depends upon a balance between tolerization of B cells by free antigen and stimulation by antigen presented by marginal‐zone macrophages. The distinction between functionally different macrophages in the spleen is elaborated in the fol

ISSN:0014-2980    

DOI:10.1002/eji.1830110310

出版商:WILEY‐VCH Verlag GmbH    

年代:1981

数据来源: WILEY

摘要:

AbstractFluorescent conjugates of hydroxyethyl (OEt) starch or Ficoll are selectively ingested and retainedin vivoby spleen marginal‐zone (MZ) and lymph node marginal‐sinus macrophages of mice, whereas similar conjugates of type 3 pneumococcal capsular polysaccharide (SIII) are generally retained by macrophages (Kupffer cells, histiocytes, macrophages of spleen, lymph nodes, bone marrow and peritoneal cavity). MZ and other macrophages are readily identifiable by fluorescence after injectionin vivoof OEt starch and SIII labeled with tetraethylrhodamine isothiocyanate and fluorescein isothiocyanate. Collagenase digestion was required for recovery of intact MZ macrophages from spleen in single cell suspensions and for maximum yields of other macrophages. MZ macrophages are larger and morphologically distinct from other macrophages, but resemble them in respect of EA, EAC receptors and acid phosphates and nonspecific esterase content and are equally radio‐resistant. They appear normal in CBA/N nude and in beige mice. Freshly isolated MZ macrophages in suspension have adherent lymphocytes, dispersible by EDTA treatment, with B but not T cell markers. It is suggested that selective adherence to MZ macrophages is a factor in determining B cell traffic. MZ macrophages did not have demonstrable surface I‐A or I‐EC antigens. Only 4–8% of other spleen macrophages freshly isolated by collagenase treatment expressed I‐A in the same preparation, whereas 35% of other cells (lymphocytes and blasts) reacted with monoclonal anti‐I‐A and anti‐I‐EC. After adherence to glass or plastic, 40% or more red‐pulp, but not MZ macrophages, became I‐A‐positive. When taken from mice recently restimulated with sheep erythrocytes, half the red‐pulp macrophages expressed I‐A even before adherence.The relation of MZ to other macrophages is not known. However, their properties are consistent with the demonstrated ability of thymus‐independent antigens selectively taken up by these cells to elicit long‐lasting IgM antibody responses by direct interaction with B cells. The unexpected observation that only a small proportion of spleen macrophages freshly isolated from unstimulated mice had detectable surface I‐A, but that this proportion was much increased after attachment to plastic, is discussed in relation to the possibility that macrophages do not express surface Ia anti

ISSN:0014-2980    

DOI:10.1002/eji.1830110311

出版商:WILEY‐VCH Verlag GmbH    

年代:1981

数据来源: WILEY