摘要:

AbstractThe gallinaceous lysozymes are a family of antigens that are distantly related to mouse lysozyme. A T cell‐dependent proliferation assay was used to characterize the spectrum of reactivities to lysozyme determinants in B10‐congenic mice. Cross‐reactivity studies using a panel of species variant lysozymes to stimulate lymph node cells from chicken egg white lysozyme‐ and ring‐necked pheasant egg white lysozyme‐primed B10.D2 mice indicated a preferential focusing of T cell reactivity onto a single determinant containing amino acids 113‐114. These data, in conjunction with results obtained by priming with cyanogen bromide cleavage fragments of lysozymes, suggested that a site common to the L3 region (amino acids 106‐129) of all the lysozymes tested was a preferential anchorage site for I region‐encoded la molecules on H‐2dantigen‐presenting cells, leading to the limited display of a determinant containing residues 113‐114.Priming with L2H (amino acids 13‐105), a peptide containing the major epitopes recognized by B10.A and B10 mice, failed to stimulate any T cell proliferation by B10.D2 lymph node cells. Thus, it appears the la molecules in any one mouse strain attach to very few sites on lysozyme to effectively display antigenic determinants for T cell activation. This result points to a model of limited determinant selection even on a very “foreign” antigen based upon a shortage of appropriate amino acid residues usable by la antigen‐pr

ISSN:0014-2980    

DOI:10.1002/eji.1830120702

出版商:WILEY‐VCH Verlag GmbH    

年代:1982

数据来源: WILEY

摘要:

AbstractEpstein‐Barr virus has been used as a B cell mitogen to explore the parallels between the B cells found in patients with hypogammaglobulinemia and the immature B cells in fetal tissues. Peripheral blood lymphocytes from 29 cases of late onset hypogammaglobulinemia (common variable immunodeficiency) and from 10 cases of X‐linked hypogammaglobulinemia were depleted of T lymphocytes and stimulated with virusin vitro.Immunoglobulin production was measured over a 4‐week culture period using inhibition radioimmunoassays for IgM, IgG, IgA and IgD. The results were compared with those seen with fetal liver cells, cord blood lymphocytes and adult lymphocytes. Virus‐stimulated cells from fetal sources produced small amounts of IgG and IgA relative to IgM, the ratio of IgM to IgG in the second week being in all cases greater than 10. Similar patterns were seen in 25/29 cases of late onset hypogammaglobulinemia, and in the eight cases of X‐linked hypogammaglobulinemia that respondedin vitro.In contrast, the ratio of IgM to IgG was always less than 8 in cultures of normal adult peripheral blood or bone marrow lymphocytes, and also in cultures from four cases of hypogammaglobulinemia known independently to have abnormal circulating suppressor cells. Eight cases of selective IgA deficiency showed reduced IgA production; six of these showed a normal ratio of IgM to IgG production. Thus, the B lymphocytes which circulate in many patients with hypogammaglobulinemia are functionally

ISSN:0014-2980    

DOI:10.1002/eji.1830120703

出版商:WILEY‐VCH Verlag GmbH    

年代:1982

数据来源: WILEY

摘要:

AbstractThe restorative potential of isogeneic and fully allogeneic thymic implants to restorein vivoantibody responsiveness to a thymus‐dependent antigen has been examined in thymectomized clawed toads. Isogeneic clones(Xenopus laevis/gilliandX. laevis/muellerihybrids) of known major histocompatibility complex (MHC) haplotypes were thymectomized at 5‐7 days, implanted with MHC‐identical or ‐mismatched (normal or irradiated) thymuses from 5‐week‐old larvae and 4 months later injected with dinitrophenylated keyhole limpet hemocyanin. IgM antibody responsiveness (measured by phage inactivation) was restored in terms of its quantity, affinity and specificity in those thymectomized animals given two haplotype‐different thymuses. Isoelectric focusing data revealed that low molecular weight antibody production was also restored with isogeneic and allogeneic thymus and that the antibody spectrotypes were of the host type. The finding thatin vivoT‐B collaboration in thymectomized animals develops normally following thymus implantation, even when the thymus genotype is disparate from the host, is discussed both in the light of previous experiments revealing MHC restriction ofXenopusT helper cellsin vitroand in terms of the role of the thymus in promoting adaptive differentiation of this ly

ISSN:0014-2980    

DOI:10.1002/eji.1830120704

出版商:WILEY‐VCH Verlag GmbH    

年代:1982

数据来源: WILEY

摘要:

AbstractTo determine whether the infrequency of immunoglobulins with λ3 light chains is due to a corresponding scarcity of λ3 B cells, the production of the various λ chain subtypes (λ 1, λ2, and λ3) by normal spleen cells was compared. The results showed that λ1, λ2, and λ3 chains are produced in a ratio of about 1.0 :0.7 : 0.3, respectively. The argument is made that λ1, λ2, and λ3 B cells exist in the same ratio. Results obtained with neonatal and nude mouse spleen cells suggest that these small differences are not due to stimulatory effects of environmental antigens or regulatory T cells. The much greater disparity in the abundance of λ subtypes in various antibody responses and serum Ig suggests that λ1 B cells may be more likely than λ2 or λ3 B cells to differentiate into antibody‐secre

ISSN:0014-2980    

DOI:10.1002/eji.1830120705

出版商:WILEY‐VCH Verlag GmbH    

年代:1982

数据来源: WILEY

摘要:

AbstractThe frequency of antigen‐specific helper T cells in human peripheral blood mononuclear cells was determined by limiting dilution analysis of specificin vitroantibody responses to influenza virus A/X‐31 (A‐H3N2). Limiting numbers of irradiated E rosette‐forming (E+) (T) cells were added to a constant number of syngeneic non‐rosette‐forming (E−) (“B”) cells and their ability to support production of antibody to influenza virus determined. The frequency of T helper cells was then calculated by a Poisson distribution analysis and found to range between 0.78 × 10−5and 2.86 × 10−5. Specific antibody production can be obtained in this system from allogeneic combination of E−and E+cells provided that the added E+cells are irradiated to abrogate alloactivated T suppressor effects. Limiting dilution analysis applied to determine the frequency of helper T cells under these conditions showed that in most, but not all, cases the frequency of T helper cells was higher in allogeneic combinations. This result could be interpreted as showing an increase in the number of activated specific T helper cells, due perhaps to a positive allogeneic effect. On the other hand, it could also be explained by the alloactivation of an entirely different subset of nonspecific helper cells, or by the production of a nonspecific allogeneic helper factor. The specificity of T cell help in allogeneic combinations was therefore examined by adding limiting numbers of E−cells to a fixed number of E−cells and simultaneously challenging with two non‐cross‐reacting influenza viruses A/X‐31 and B/HK. Under these conditions, individual cultures produced antibody to A/X‐31, B/HK or both. The frequency of cultures producing antibody to both viruses was as predicted for the chance occurrence of specific helper T cells for both antigens being present in the same culture. The fact that a significant number of individual cultures made antibody to only one antigen in both autologous and allogeneic combinations showed that T cell help was antigen‐specific in both situations. Thus, for humanin vitroantibody responses, antigen‐specific T cell help can be obtained across a m

ISSN:0014-2980    

DOI:10.1002/eji.1830120706

出版商:WILEY‐VCH Verlag GmbH    

年代:1982

数据来源: WILEY

摘要:

AbstractImmunoglobulin isotype expression in isolated lymph node (LN), spleen and blood lymphocyte suspensions was assessed in rats. The proportion of μ+δ−B cells in spleen (34%) was approximately twice that in blood and LN. Immunohistological examination of spleens showed the cells of the marginal zones to be predominantly μ+δ−. On the other hand, μ+δ+B cells were mainly confined to the follicles in both spleen and LN. These follicles had a minor μ+δ−component.The migratory properties of B cells with these two phenotypes were assessed by depleting lymphocytes migrating through the white pulp of rat spleen. This was achieved by placing a32P‐impregnated β‐emitting polythene strip over one half of the spleen. Examination of the nonirradiated half of the spleen, LN and peripheral blood after 12 days irradiation showed selective loss of δ+B cells. The μ+δ−cells of the splenic marginal zone were numerically unaltered. There was also a substantial residual μ+δ−B cell presence in the small lymphocyte compartment of follicles of LN and spleen in depleted animals. In addition, the blood selectively retained a μ+δ−B cell component. This was not derived from the spleen, as μ+δ−blood B cell numbers were sustained even where both halves of the spleen were irradiated. It is concluded that: (a) the major static B cell component of spleen and LN is μ+δ−, (b) that most if not all δ+B cells repeatedly migrate through the spleen and (c) there is a blood‐born μ+δ−component which is

ISSN:0014-2980    

DOI:10.1002/eji.1830120707

出版商:WILEY‐VCH Verlag GmbH    

年代:1982

数据来源: WILEY

摘要:

AbstractA cell surface lectin found on activated human lymphoid cells has been identified and characterized using membrane glycoprotein micelles as probes. These micelles, which are large, water‐soluble aggregates, are composed of glycoproteins isolated from detergent‐solubilized membranes of human B lymphoblastoid cell lines byLens culinarishemagglutinin affinity chromatography. The micelles have an average apparent molecular weight of 4 × 106estimated by gel filtration and range in diameter from 25‐100 nm. Micelles bind to B and T lymphoblastoid cell line cells and peripheral blood lymphocytes activated with concanavalin A or in a mixed lymphocyte response. Unactivated peripheral blood lymphocytes and red blood cells bind very low levels of the micelles. The binding is saturable, reversible, and temperature‐dependent, with poor binding below 15 °C. Glycoproteins such as fetuin and porcine thyroglobulin, which contain complex oligosaccharide side chains, inhibit the binding, whereas glycoproteins containing only high mannose or simple serine‐linked carbohydrate side chains do not. In addition, binding can be inhibited by complex asparagine‐linked glycopeptides purified from pronase‐digested fetuin, but not by the simple serine‐linked glycopeptides. Membrane glycoprotein micelles are bound to the surface of the cells but are not internalized or degraded. The potential role of this cell surface lectin in lymphocyte func

ISSN:0014-2980    

DOI:10.1002/eji.1830120708

出版商:WILEY‐VCH Verlag GmbH    

年代:1982

数据来源: WILEY

摘要:

AbstractAthymic (nude) rats were found to have increased levels of natural killer (NK) activity, 3− to 5−fold higher than in euthymic rats. Studies were performed to determine the nature of the NK cells in these animals and the basis for their increased cytotoxic reactivity. Large granular lymphocytes (LGL), which were previously shown to be the NK cells in euthymic rats, were increased 2‐ to 7‐fold in the peripheral blood and spleen of nude rats. The LGL, enriched by centrifugation on discontinous Percoll density gradients, were shown to have augmented NK activity similar to that seen with LGL‐enriched fractions from euthymic rats. These results indicate that the NK cells in euthymic and athymic rats are morphologically and functionally similar, and that the higher NK activity in nude rats appears to be mainly attributable to an increased proportion of effector cells. In a single‐cell cytotoxicity assay, interferon pretreatment of LGL was shown to increase: (a) the percentage of LGL which form conjugates with target cells; (b) the percentage of conjugate‐forming cells which kill; and (c) the kinetics of lysis. Different effects were seen depending on the targe

ISSN:0014-2980    

DOI:10.1002/eji.1830120709

出版商:WILEY‐VCH Verlag GmbH    

年代:1982

数据来源: WILEY

摘要:

AbstractOn the basis of reports that deoxyguanosine is selectively toxic for adult T lymphocytes, the usefulness of this compound in the production of lymphocyte‐depleted embryonic thymus rudiments in anin vitroorgan culture system was investigated. The results showed that a period of exposure to deoxyguanosine causes depletion of the lymphoid cells while the stromal elements continue to survive, with many of the cells showing an epithelial morphology and expression of I region products of the major histocompatibility complex (MHC). When associated with either fetal liver or another thymus fragment as a source of T cell precursors in transfilter experiments, these “empty” thymuses become recolonized, enabling the production of chimeric thymus with stromal and lymphoid cells of different haplotypes. In combination with functional assays, this system offers an entirelyin vitroapproach to questions relating to the repertoire potential of T cell precursors from different sources and the role of the thymus in tolerance and MHC restri

ISSN:0014-2980    

DOI:10.1002/eji.1830120710

出版商:WILEY‐VCH Verlag GmbH    

年代:1982

数据来源: WILEY

摘要:

AbstractLarge granular lymphocytes (LGL) are a subpopulation of human peripheral blood mononuclear cells believed to contain the mediators of spontaneous cytotoxicity or natural killing. In the present study, the mononuclear cells were enriched for LGL by differential density centrifugation on Percoll gradients and examined by transmission electron microscopy. The ultrastructure of LGL and of their binding interaction with natural killer‐susceptible target cells (K562) is described in detail. Some morphological similarity between LGL and cells of a myelocytic origin was observed. Studies reported elsewhere have shown that Sr2+, an alkaline earth ion known to degranulate granulocytes, inhibits NK cell function. Comparison of the morphology of control and Sr2+‐treated LGL showed that Sr2+caused several characteristic changes in LGL ultrastructure and, indeed, led to their degranulation. The recovery of natural killer function seen followingin vitroculture of Sr2+‐treated effector cells was accompanied by the reappearance of typical intracytoplasmic granules. These data strongly suggest that the granules of LGL are required for and, perhaps, involved in natural killer‐mediated cy

ISSN:0014-2980    

DOI:10.1002/eji.1830120711

出版商:WILEY‐VCH Verlag GmbH    

年代:1982

数据来源: WILEY