bluuebunny/crossref_metadata_2025 huggingface dataset:
Human Ia‐Like Antigens Associated with HLA‐D
Authors: ALBRECHTSEN D. , SOLHEIM B. G. , THORSBY E.
Published: June 2006

Antisera raised within HLA‐A‐ and ‐B‐compatible, HLA‐D‐disparate combinations were cytotoxic to B lymphocytes from the immunizing donor and to B lymphocytes from most or all cell donors sharing the immunizing donor's HLA‐D phenotype. Four antisera recognized structures closely associated with the HLA‐D determinants Dw2, Dw3, Dw4, and LD 108. One antiserum had a broad reactivity pattern, including Dw3, Dw6, and some unknown specificity(ies). In population and family studies these B‐lymphocyte antigens behaved as if they were governed by one genetic locus in the B‐D region of the HLA complex. Furthermore, the antisera were cytotoxic to a minor concanavalin‐A‐reactive T‐cell subpopulation. The antisera had previously been shown to inhibit the stimulating cells in mixed lymphocyte culture and to be capable of inhibiting the Fc receptor in the EA rosette assay. We conclude that the antisera produced by this method recognize Ia‐like antigens closely associated with the HLA‐D determinants.
B‐ and T‐Cell‐Specific Alloantigens in Man
Authors: ALBERT E. D. , ANDREAS A. , McNICHOLAS A. , SCHOLZ S. , KUNTZ B.
Published: June 2006

Screening for B‐cell‐specific antibodies in unabsorbed pregnancy sera preselected for weak reactivity in regular HLA‐A, ‐B, and ‐C screening yielded a relatively high proportion (35/81) of B‐cell‐specific antibodies. Most B‐cell‐specific antibodies react broadly, showing inclusion phenomena suggesting ‘cross‐reactivity’ analogous to that observed in HLA‐A and ‐B serology. In control experiments with T‐cell‐enriched suspensions three antisera reacted with T cells and not with B cells. These antisera are highly associated with HLA‐A2 in the unrelated population and segregate with HLA haplotypes in families and with HLA‐A in a family with HLA‐A, B recombination. Thus it appears that the human equivalents of la antigens may include—in analogy to the murine Ia antigens—B‐cell‐ as well as T‐cell‐specific alloantigens.
Cytotoxic Effect of Anti‐H‐2 and Anti‐Ia Antisera on Human B and T Cells
Authors: IVÁNYI P. , GYÓDI E. , GYÖRFFY GY. , PAVLJUKOYÁ H. , IVAŠKOVÁ E. , PETRÁNYI GY.
Published: June 2006

Anti‐H‐2 and anti‐Ia alloimmune mouse antisera were tested by the microcytotoxicity test on human peripheral blood B‐ and T‐cell preparations. Anti‐H‐2 antisera react by a higher titer and/or cytotoxicity scoring grade on B cells than on T cells. Anti‐Ia antisera react practically only with B cells. It was assumed that anti‐H‐2 antisera contain two components. One component reacts specifically with certain HLA‐A‐or ‐B‐locus antigens or other closely linked gene products. The other component reacts predominantly or only with B‐cell determinants; the specificity of the latter component has not yet been studied in sufficient detail.
Cellular Distribution, Purification, and Molecular Nature of Human la Antigens
Authors: SNARY D. , BARNSTABLE C. J. , BODMER W. F. , GOODFELLOW P. N. , CRUMPTON M. J.
Published: June 2006

Human Ia antigens were extensively purified (1390‐fold increase in specific activity) in 32% yield from BRI8 cells, a lymphoblastoid B‐cell line. Purification was monitored by using allogeneic antisera arising by foetal‐maternal stimulation. The product, a glycoprotein fraction, contained the la antigens, the HLA‐A and ‐B antigens, and a glycoprotein of unknown function. The glycoptotein fraction was composed of four glycosylated polypeptides with molecular weights of 43,000, 39,000, 33,000, and 28,000, and β2‐microglobulin; no polypeptide was linked to another by disulphide bridges. The A and B antigens only were absorbed by antibody against β2‐microglobulin. The Ia antigens comprised one each of the 33,000 and 28,000 molecular weight glycosylated polypeptides noncovalently linked together. Thus, only these chains were absorbed by xenogeneic anti‐Ia antisera and were cross‐linked by dimethyl‐3–3′‐dithiobispropionimidate dihydrochloride. The dimeric molecule bound deoxycholate (0.26 g/g of protein) and, when solubilized in deoxycholate, has a molecular weight of 77,000. The Ia allo‐ and xeno‐antigenic activities were labile to heating and proteolysis and are probably determined by the polypeptide structure. Xenogeneic specific anti‐Ia antisera were raised in rabbits and mice by immunizing with the glycoprotein fraction. These antisera reacted with B lymphocytes and monocytes but not T lymphocytes and fibroblasts. Their Fab fragments blocked the cytotoxicity of the allogeneic antisera for B lymphocytes and were potent inhibitors of the mixed lymphocyte reaction.
Three‐Point Association of HLA‐A,B,Bf Haplotypes Deduced in 200 Parents of 100 Families
Authors: ALBERT E. D. , RITTNER C. , SCHOLZ S. , KUNTZ B. , MICKEY M. R.
Published: June 2006

The association of HLA‐A and ‐B antigens with Bf alleles was investigated in 200 parents from 100 unrelated families. There were significant associations between HLA‐A3 and Bf‐F, B7 and Bf‐S, B8 and Bf‐S, B12 and Bf‐F, and BW35 and Bf‐F. Three‐point HLA‐A,B,Bf haplotype frequencies, linkage disequilibrium parameters, and chi‐square values were determined both from the genotype and from the pheno‐type data. Although the HLA‐B,Bf associations involve antigens that are also present in the highly associated A,B and B,D haplotypes of the Caucasian population, there was—with the possible exception of HLA‐A3,B7,Bf‐S–no significant three‐point association for HLA‐A,B,Bf.
Relationship Between Fc Receptors and Ia Alloantigens: Analysis with a Sensitive Radioimmunoassay
Authors: RIEBER E. P. , WERNET P.
Published: June 2006

This paper describes the successful use of 125I‐labeled IgG aggregate to detect Ia‐type alloantibodies in pregnancy sera. The blockade of aggregate uptake of a variety of normal mononuclear and leukemic cell types by anti‐Ia alloantibodies is analyzed. Fc receptors and Ia alloantigens are clearly two distinct molecular entities. The association between Fc receptors and Ia alloantigens on a quantitative level seems to depend on a ligand‐binding mechanism to control their interaction rather than the presence of a topographical molecular tandem arrangement.
Response of Primed LD Typing Cells to Homozygous Typing Cells
Authors: BACH F. H. , BRADLEY B. A. , YUNIS E. J.
Published: June 2006

At least two different methods using cellular responses have been described for defining the determinants of the HLA‐D region: typing with HLA‐D homozygous cells and primed LD typing. Primed LD typing cells were generated in one‐haplotype‐different combinations and grouped on the basis of two or more cells appearing to define the same HLA‐D‐region‐determined PL antigen. Such cells were restimulated with homozygous typing cells for several of the presently known HLA DW clusters. A very strong correlation was noted: PLT cells defining the antigen PL1 were restimulated with homozygous typing cells for DW3, those PLT cells defining the antigen PL2 were restimulated by homozygous typing cells for DW2, and those defining PL5 were restimulated by homozygous typing cells for DW1.
Detection of HLA‐D Clusters Using Primed LD Typing
Authors: CROSIER P. S. , SASPORTES M. , MAWAS C. , CHARMOT D. , DAUSSET J.
Published: June 2006

Using a set of 17 primed LD typing (PLT) cells tested on n panel of 35 unrelated cells, we showed that certain groups of PLT cells tended to detect similar unrelated cells. The PLT cells were grouped into seven clusters and these tended to correlate with the seven HLA‐D specificities represented on the panel, as determined by HTC testing. These data suggest that the antigens that cause restimulation in PLT are similar to those HLA‐D antigens detected by the homozygous typing cell (HTC) test or, alternatively but more unlikely, that the two typing methods are detecting genes in close linkage disequilibrium with the HLA‐D region.
Typing an Unrelated Panel with PLT Cells: Association with DW Clusters
Authors: ALTER B. J. , BACH F. H. , JARAMILLO S. , WERNET P.
Published: June 2006

Primed LD typing (PLT) cells prepared in one laboratory (Madison) were shipped in the frozen state and tested in Tübingen on a separate panel that bad been typed with homozygous typing cells. Those PLT cells that had been grouped, on the basis of their reaction with rest cells of the Madison panel, as defining an HLA PI antigen showed identical or nearly identical patterns of reactivity with the Tübingen panel. Clear association between certain PL antigens and DW clusters as defined with homozygous typing cells could be demonstrated. Of particular interest may be combinations of certain PLT reactions with D‐locus‐typed cells, where the primed cells do not react as expected from the target's HLA‐D type.
Cellology of HLA I. The Apparent Homogeneity of HLA‐D
Authors: TERMIJTELEN A. , BRADLEY B. A.
Published: June 2006

We have demonstrated that there is a similarity in the distribution of restimulation response of primed lymphocyte typing (PLT) cells raised between related and unrelated individuals, thus leading to the suggestion that HLA‐D is a homogeneous determinant. It is proposed that within HLA a hitherto unrecognized heterogeneous structure may exist that is closely associated wish HLA‐D and which may give rise to intermediate reactions in primary mixed lymphocyte reactions and PLT.
Cellology of HLA II. Heterogeneity of Cellular Reactions in Negative HLA‐D Typing
Authors: BRADLEY B. A. , TERMIJTELEN A.
Published: June 2006

We have demonstrated that in more than half of the mixed lymphocyte reactions, proliferative reactions, in which responders were reacted against HLA‐D‐compatible homozygous typing cells, were significantly greater than zero. These reactions often masked the true HLA‐D identity of the cells under test, as was subsequently shown by primed lymphocyte testing.
Lack of Restimulation by Non‐HLA Antigens in Primed Lymphocyte Typing
Authors: SHIH C.‐Y. , VALENTINE E. A. , SHEEHY M. J. , SONDEL P. M. , BACH F. H.
Published: June 2006

We have studied the role of non‐HLA antigens in restimulation of PLT cells by the following protocols. Responder cells were sensitized to cells from family members differing by one HLA haplotype. These PLT cells were restimulated by family members HLA‐ or HLA‐D‐identical to the responder. In none of these cases did we find significant restimulation, indicating that it is unlikely that there is a restimulatory non‐HLA locus with even two alleles (p < 0.05) of equal frequency. Other protocols we have used are consistent with this interpretation. This indicates that antigens determined by genes segregating independently of HLA do not play a major role in the PLT restimulation.
Detection by Three Cellular Immunological Techniques of the Antigenic Determinants of the Ly‐Li System, Expressed on Human B Lymphocytes
Authors: SASPORTES M. , MAWAS C. , CROSIER P. , CHARMOT D. , LEGRAND L. , DAUSSET J.
Published: June 2006

A clear correlation was observed between the presence of an Ia‐like antigenic B‐cell system Ly‐Li, detected serologically, and three cellular immunological techniques: [1] mixed lymphocyte reaction (MLR) inhibition by an anti‐Li antiserum; [2] level of restimulation of anti‐Ly‐Li in‐vitro‐primed lymphocytes; and [3] detection of HLA‐D alleles by homozygous typing cells. These results suggested that the allelic products detected serologically may be identical to those detected by the first two techniques, namely MLR inhibition and in‐vitro‐primed lymphocyte typing, and, possibly, HLA‐D typing using homozygous typing cells, although the correlation was repeatedly found to be less clear for the last technique.
Selection of Haploid Spermatozoa and Its Application to HLA‐D Typing
Authors: FESTENSTEIN H. , HALIM K. , ARNAIZ‐VILLENA A.
Published: June 2006

The expression of HLA‐A, ‐B, and ‐D determinants on the surface of spermatozoa is haploid. Using cytotoxicity and appropriate HLA antisera and complement, we were able to select haploid spermatozoa. The surviving sperms behaved similarly to homozygous lymphoid cells when cultured in mixed sperm lymphocyte culture (SLC). This method is being applied to define new HLA‐D specificities, to improve typing and matching for bone marrow transplantation and kidney transplantation and to study their association with various diseases.
Apparent Lack of Gene Dosage Effect in the PLT Assay
Authors: JARAMILLO S. , ANHORN G. , SCHUNTER F. , WERNET P.
Published: June 2006

In this paper the results of primed lymphocyte typing (PLT) tests are reported which show the response to HLA‐D‐specific stimulator and to unrelated cells. The aim was to find out the sensitivity of the PLT method for evaluating not only qualitative HLA‐D‐region differences but also gene dosage effects. In addition, the primed cells were restimulated with cells from HLA‐D‐homozygous individuals mutually negative with the specific stimulator in the usual 5‐day primary mixed lymphocyte culture incubation. No gene dosage effect in PLT experiments could be observed.
Mechanisms of the H‐2 Effect on Viral Leukemogenesis
Authors: BUBBERS J. E. , BLANK K. J. , FREEDMAN H. A. , LILLY F.
Published: June 2006

Evidence has been gathered which supports the notion that two distinct but interacting mechanisms, controlled by loci mapping within the H‐2 complex, influence Friend murine leukemia virus (FV) disease. One mechanism, controlled by a gene mapping in or close to H‐2D, influences the capacity of the H‐2D gene product to form molecular complexes with FV molecules in the plasma membrane of infected cells. Formation of a complex appears to provide a target antigen for syngeneic cytotoxic T‐lymphocytes, to cause co‐capping of FV and H‐2D antigens, to permit the selective inclusion of H‐2Db molecules into progeny Friend virions, to influence the long‐term maintenance of virus production in vitro and, in conjunction with the second mechanism, to stimulate the generation of cytotoxic T‐lymphocytes. This second mechanism is controlled by a gene in the H‐2K or H‐2I region, and, in the presence of an H‐2/FV molecular complex immunogen, influences the generation of H‐2 restricted cytotoxic T‐lymphocytes and the rate of rejection of syngeneic FV‐induced tumor cells.
Emergence of Foreign H‐2‐Like Cytotoxicity and Transplantation Targets on Vaccinia and Moloney Virus‐Infected Meth. A Tumour Cells
Authors: MATOSSIAN‐ROGERS A. , GARRIDO F. , FESTENSTEIN H.
Published: June 2006

Using cytotoxic effector cells of different anti‐H‐2 specificities, new cell‐mediated lympholysis targets, normally undetected on Meth. A tumour cells, were shown after passage with vaccinia or Moloney virus. The H‐2d CML targets on Meth.A cells recognized by B10.BR anti‐B10.D2 effector cells were presented only after simultaneous vaccinia virus passage, while passage with Moloney virus caused the emergence of H‐2b targets. Small but significant killing of vaccinia virus‐passaged Meth.A was also obtained by anti‐H‐2k effector cells. These results are discussed in relation to in vivo experiments: retardation of tumour growth was noted in mice which had received several injections of vaccinia or Moloney virus, shoving that the new CML targets were probably acting as transplantation targets.
Responses of Alloantigen‐Primed Lymphocytes in Vitro The Specificity of Secondary Responses Assayed by Titration of Primed Lymphocyte Populations
Authors: CORLEY R. B.
Published: June 2006

Maximal proliferative responses were observed ac lower responder cell densities in alloantigen‐primed lymphocyte populations when restimulated with the specific priming cell than when restimulated with other allogeneic cells. This relationship was due to the larger number of lymphocytes within the primed population which responded to the specific sensitizing cell than to unrelated stimulator cells. As a result, at high response cell densities, stimulator cells unrelated to the specific sensitizing cells elicited a disproportionately high response relative to the rwpoiwe stimulated by the specific cells. Restimulation of decreasing number of primed lymphocytes gave a more accurate representation of the stimulatory capacity of different cells. Because primed populations contain a larger number of lymphocytes that respond to the specific stimulator than to other Stimulators, responses of primed lymphocytes could be made operationally monospecific. Limiting dilution analysis demonstrated that low numbers of primed cells were stimulated by the specific sensitizing cells but not by unrelated stimulator cells.
Tolerance Induction to H‐2 Central Region Target Antigens: In Vivo/in Vitro Correlations
Authors: KUPERMAN O. J. , SOLLINGER H. W. , BACH F. H.
Published: June 2006

Tolerance was induced against cytotoxic target determinants coded for by genes of the I region. Neonatal recipients were immunized with high doses of cells from an I region incompatible donor. Nonreactivity in adult life did not reflect extensive donor cell chimerism, since the great majority of cells in spleens of animals rendered tolerant were of host phenotype. Although specific nonresponsiveness in CML could be induced by these protocols, the MLC proliferative response was in most cases still present although very much decreased. In only a very occasional animal was complete nonreactivity in MLC seen. The nonresponse in CML was paralleled by acceptance of thyroid allografts as measured by radioactive iodine incorporation and morphological studies.
Human Ia Alloantigens as Cell‐Differentiation Markers of Normal and Pathologic Leukocyte Surfaces
Authors: WERNET P. , BETSCH C. , BARTH P. , JARAMILLO S. , SCHUNTER F. , WALLER H. D. , WILMS K.
Published: June 2006

Comparative membrane phenotypes of normal T and B lymphocytes, of normal myeloid cells, and of various leukemic cell types were established by the use of specific Ia‐type alloantisera and ‘classical’ immunological surface markers, including complement receptors. 4%–8% of lymphocytes taken from mixed leukocyte cultures on day 4 showed Ia alloantigens of responder‐type specificity, in addition to two known T‐cell markers on the same cell surface. Together with Ia antiserum inhibition studies, this subpopulation would appear to present a human mixed leukocyte culture (MLC)‐related suppressor T‐cell population. Whilst such cells could not be detected in normal peripheral blood by double fluorescence, a small percentage could readily be demonstrated among cell populations from patients with systemic lupus erythematosus and rheumatoid arthritis (joint fluid). Specific Ia alloantigens were further detected on the immature myeloid cells from bone marrow but not on the more mature myeloid cell types. This establishes the Ia alloantigen system as a valuable cell surface differentiation marker in man. The appearance of complement receptors on myeloid cells was Later than that of Ia alloantigens. Ia alloantigens are expressed on various numbers of leukemic myelo‐ and lympho‐blasts of the so‐called ‘non‐T, non‐B’ cell types. After discontinuous Ficoll gradients to enrich specific density cell groups, mainly the Ia alloantigens and the complement receptors allow a discrimination between acute (AML) and chronic myelocytic leukemia (CML) blasts, inclucling blasts crisis cells. AML cells appear to present a less differentiated cell type than CML blasts crisis cells. For the Latter disease, a more complex picture is obtained since at least three different membrane phenotypes of blasts cells can be identified: an Ia‐positive and an Ia‐negative myeloid blasts and an Ia‐positive lymphoid blasts. The relative quantities of these three elements can vary considerably within even a small group of patients.
In Vitro TNP‐Specific Antibody Formation by Peripheral Lymphocytes from Patients with Systemic Lupus Erythematosus
Authors: MORIMOTO C. , ABE T. , HARA M. , HOMMA M.
Published: June 2006

Immunological reactivity in patients with systemic lupus erythematosus (SLE) was assessed by investigating in vitro trinitrophenyl (TNP)‐specific antibody formation by peripheral lymphocytes. Peripheral lymphocytes from 16 patients with SLE were cultured with TNP conjugated with horse erythrocytes (TNP–HRBC) in the presence of 2‐mercaptoethanol. The hemolytic plaque assay was used to detect hapten (TNP)‐specific antibody‐forming cells. Peripheral lymphocytes from normal individuals failed to produce antibody to TNP, whereas SLE lymphocytes produced a significant number of plaque‐forming cells. Co‐culture experiments with SLE and normal lymphocytes suggested that patients with SLE have a defect in T lymphocytes, leading to abnormal antibody production.
Participation of C3 in Intracellular Killing of Candida albicans
Authors: YAMAMURA M. , VALDIMARSSON H.
Published: June 2006

Using new objective methods for measuring, independently, phagocytosis and killing, it was demonstrated that Candida albicans opsonized by C3‐deficient serum was ingested but not killed in vitro by human polymorphonuclear leukocytes. Killing could be induced by adding purified C3 to the C3‐deficient serum. It is concluded that C3 participates directly in the intracellular process leading to phagocytic killing of C. albicans.
Isolation of IgG3 from Polyclonal Human IgG by Affinity Chromatography with Ricinus Agglutinin
Authors: SALTVEDT E. , NATVIG J. B.
Published: June 2006

Ricinus agglutinin purified to homogeneity reacts with serum glycoproteins containing terminal nonreducing galactose residues, including about 10% polyclonal IgG. To study the IgG subclass distribution of this reaction, four monoclonal IgG1 proteins, two IgG2, four IgG3, and two IgG4 proteins were tested by affinity chromatography experiments with insolubilized ricinus agglutinin. Only the IgG3 proteins reacted, and the reactive sites were localized to the Fc fragment. Passage of polyclonal human IgG through a ricinus agglutinin–Sepharose column, followed by elution with lactose, permitted the isolation of IgG3 from normal polyclonal IgG.
Grenetic Control of Primary and Secondary IgG Responses to Sheep Erythrocytes in Mice
Authors: ANDO I. , FACHET J.
Published: June 2006

The genetic control of the primary and secondary IgG responses to sheep erythrocytes has been studied by using inbred, H‐2‐congenic, and intra‐H‐2‐recombinant mouse strains. According to our results, the primary IgG respone is under multi‐genic control. There is a correlation, however, between the titer of primary IgG antibodies produced and the H‐2 phenotypes among the mouse strains tested. One H‐2‐linked gene maps at the I‐B subregion, whereas another gene can be mapped at or closely linked to the H‐2D region. Low and high responsiveness were associated with H‐2b, H‐2f and H‐2a, H‐2d, H‐2k phenotypes, respectively. By comparison of the responses of inbred and congenic strains having the same H‐2 phenotype, it can be concluded that background genes influence the primary response only slightly but have almost complete control over the secondary response.
Responses of Alloantigen‐Primed Lymphocytes In Vitro The Contribution of Increased Frequencies of Responding Lymphocytes to Differences Between Reactivity of Normal and Primed Lymphocyte Populations
Authors: CORLEY R. B.
Published: June 2006

Sensitization of lymphocytes against allogeneic cells in vitro results in significant enrichment of alloreactive lymphocytes. Such enrichment was found to profoundly influence the Conditions for measuring proliferative responses. Fewer primed lymphocytes than unprimed ones had to be cultured to favor optimal proliferation. Second, proliferate responses could be detected using 10 to 20 times fewer primed responding cells than when using unprimed responders. Finally, although responses of both unprimed and primed lymphocytes were dependent on the number of stimulator cells in culture, the primary mechanism(s) through which this dependence was expressed appeared to differ. The results demonstrate that, under the same conditions, comparisons of responses of two populations that contain different proportions of reactive lymphocytes may not be justified.
Oligoclonal Measles Virus‐Specific IgG Antibodies Isolated from Sera of Patients with Subacute Sclerosing Panencephalitis
Authors: VANDVIK B.
Published: June 2006

Measles virus‐specific antibodies isolated from sera of six patients with subacute sclerosing panencephalitis (SSPE) were all composed of oligoclonal IgG proteins, in contrast to the polyclonal IgG antibodies isolated from sera of healthy individuals. Periods of disease progression were associated with an increase in number and amount of oligoclonal IgG antibody proteins, and a decrease was observed in disease remission. A correspondence between the oligoclonal measles‐specific IgG of serum and the oligoclonal IgG proteins of cerebrospinal fluid (CSF) occurred in each case. It is concluded that sera from patients with SSPE may be used instead of CSF as a source for the isolation of measles antibodies of restricted heterogeneity.
IgG1 Subclass Restriction of Oligoclonal Measles Virus‐Specific IgG Antibodies in Patients with Subacute Sclerosing Panencephalitis and in a Patient with Multiple Sclerosis
Authors: VANDVIK B. , NATVIG J. B. , NORRBY E.
Published: June 2006

A restriction to the IgG1 subclass was demonstrated for measles virus‐specific IgG antibodies isolated from the sera of five patients with subacute sclerosing panencephalitis, from the cerebrospinal fluid of one of the patients, and from brain extract from a sixth patient. A predominance of IgG1 was also observed in measles antibodies isolated from the serum and brain extract of a patient with multiple sclerosis. Evidence is presented that the IgG1 restriction is associated with the occurrence of oligoclonal measles antibodies in these patients. A similar restriction to the IgG1 subclass was not observed in measles antibodies isolated from the serum of a measles‐convalescent child or from pooled normal serum and IgG.
Occurrence of Amyloid‐Related Serum Proteins in Patients with Benign Monoclonal Gammopathy
Authors: HUSBY G. , LINDSTRÖM F. D. , NATVIG J. B. , DAHLSTRÖM U.
Published: June 2006

The serum protein SAA, which is related to the amyloid fibril protein AA, was detected by double immunodiffusion using anti‐protein AA antiserum. The SAA level was elevated in 16 of 32 patients with benign monoclonal gammopathy (BMG). In addition, two BMG sera reacted with an antiserum to amyloid fibril protein of immunoglobulin light‐chain type, VλJ (EF), and one reacted with anti‐amyloid protein VλV (AR). The reactivity of the BMG sera with antisera to the various amyloid fibril proteins was strikingly similar to that of 35 sera from patients with myelomatosis. In the age group of 50–70 years the proportion of SAA‐positive sera in BMG (53%) and myelomatosis (56%) was strikingly higher than that of the normal controls (5%). In older subjects (70–90 years), however, the frequency of SAA in BMG or myelomatosis, although increased (53%–54%), was not significantly greater than that of a control group of apparently healthy individuals (44%).
The Major Histocompatibility Complex: Influence on Immune Reactivity and T‐Lymphocyte Activation
Authors: Miller J. F. A. P. , Vadas M. A.
Published: June 2006

The genetic region that influences graft rejection in animals and man is known as the major histocompatibility complex (MHC). The gene products of this complex (15) exert a profound influence on the activation of T lymphocytes. At least three effects of the MHC on T cells deserve special mention. First, the frequency of T lymphocytes that respond to cell surface alloantigens coded by the MHC is 100 to 1000 times greater than the frequency of T cells that respond to other antigens (27, 35). Second, the extent of a T‐cell response to certain antigens is controlled by genes that have been mapped in the I region of the MHC (3). Third, it has recently been shown that the MHC imposes constraints on the activities of sensitized T cells (7). The aim of this article is to review briefly some of the recent work performed in mice which allows the formulation of a model that may be used to explain tentatively the relationship between MHC gene products, T‐lymphocyte activation, and immune reactivity.
Macrophage‐Dependent Response of Immune Human T Lymphocytes to PPD In Vitro Influence of HLA‐D Histocompatibility
Authors: BERGHOLTZ B. O. , THORSBY E.
Published: June 2006

The proliferative response of immune human T lymphocytes to low concentrations of purified protein derivative (PPD) in vitro was found to require the presence of macrophages. By coculturing different combinations of immune T lymphocytes and allogeneic macrophages with PPD in low concentration, optimal stimulation (that is, as efficient as the autologous combinations) was shown to require HLA‐D identity between the macrophages and responding T cells. Identity for HLA‐A and ‐B appeared to be of less or no importance. It is concluded that membrane structures encoded by HLA‐D or closely linked loci are involved in the human macrophage/T‐lymphocyte interaction in the proliferative response to PPD, much in the same way as the Ia antigens of rodents.
Evidence of ‘K’‐Cell Killing by Alloactivated, Fc‐Receptor‐Bearing Cytotoxic T Lymphocytes
Authors: KIMURA A. K. , RUBIN B. , ANDERSSON L. C.
Published: June 2006

Upon in vivo alloactivation of Ig‐anti‐Ig column‐purified splenic ‘T’ cells in lethally irradiated allogeneic recipients, a variable proportion of donor‐derived cytotoxic T lymphocytes (CTLs) are able to bind IgG antibody‐coated erythrocytes through surface Fc receptors (FcR) and form rosettes. The use of fractionation procedures based on the ability of these cells to form rosettes has enabled us to separate FcR‐positive CTLs from FcR‐negative CTLs and to examine the ability of these two cell populations to perform as effector cells in direct T‐cell‐mediated killing and in antibody‐dependent cellular cytotoxicity. A series of experiments, either by direct isolation of the two cell populations or by deletion of the FcR‐positive population by filtration through complexed immunoglobulin columns (Ig‐anti‐Ig), has shown both populations to be efficient in direct T‐cell mediated cytotoxicity against the relevant target cell. The striking difference between the two populations is the exclusive ability of the FcR‐positive population to function as effector cells in antibody‐dependent cellular cytotoxicity (ADCC). Purification steps before in vivo alloactivation of our responding cells for the removal of ‘B’ cells and FcR‐bearing cells with‘K’‐cell activity, followed by procedures to remove phagocytic and adherent cells in the resulting immune spleen cell preparation and, finally, by velocity sedimentation of the rosetting and nonrosetting blasts from the small lymphocyte population, has resulted in a population of FcR‐positive cells 98% positive for the Thy 1.2 alloantigen. These fractionation steps and immnunofluorescence criteria of purity strongly favor the contention that the ADCC activity within the FcR‐positive T‐cell population is indeed a property of the CTL itself.
Activation of Human Suppressor Cells in Mixed Lymphocyte Cultures
Authors: HIRSCHBERG H , THORSBY E.
Published: June 2006

Lymphocytes transferred from 6‐day‐old human mixed lymphocyte cultures (MLC) inhibited the response to allogeneic cells of freshly taken lymphocytes autologous to the transferred MLC‐responding cells. No specificity for this cell‐dependent suppression could be determined. The inhibitory effects of the suppressing cells could be abrogated by moderate X‐ray irradiation and significantly reduced by pretreating them with an anti‐Ia‐like antiserum and complement, Tin‐human suppressor cell responsible for the observed effects therefore appears to carry determinants equivalent to the murine Ia alloantigens.
Prolonged Survival of Implanting Rat Blastocysts in the Uterus of Congenitally Athymic Mice
Authors: HAKANSSON S. , LUNDKVIST ö. , NILSSON ö. , ALM G.
Published: June 2006

Rat blastocysts were transferred to the uteri of either immunodeficient, congenitally athymic (nu/nu) ‘nude’ mice or immunocompetent, heterozygous (nu/+) mice. Histological analysis showed that there was a similar frequency of implanted blastocysts in the two types of mice, that blastocysts transferred to nude athymic mice outlived those in heterozygous controls by at least 3 days, and that blastocysts in nude mice showed delayed and abnormal development and were eventually rejected. These findings suggest that the T‐cell deficiency in nude mice may prolong the survival of implanting blastocyst but that other immune or non‐immune factors still limit their development.
Antibody‐Dependent Cell‐Mediated Cytotoxicity in Various Orders of Vertebrates
Authors: IMIR T. , SAKSELA E. , MÄKELÄ O.
Published: June 2006

By using chicken antibodies and chicken lymphoid cells, we could demonstrate antibody‐dependent cytotoxicity (ADCC) against haptenated chicken erythrocytes. ADCC could be demonstrated either by treating the target cells with antibody (sensitization) or by treating the effector cells (arming). Approximately ten times higher antibody concentrations were required for arming than for sensitization. Chicken lymphoid cells did not co‐operate with mammalian antibodies in either type of ADCC, and thus the situation was reciprocal to that observed earlier with mammalian lymphoid cells. In a further attempt to characterize the arming phenomenon we used biofiltered (aggregate‐free) mouse antibodies for the arming of rat spleen cells. They were as efficient as nonfiltered antibodies, and this confirms that individual antibody molecules are efficient in arming.
In Vitro Cross‐Reacting Antibodies from Rabbit Antisera to Rat Brain Synaptic Membranes and Thymocytes
Authors: JANKOVIĆ B. D. , HORVAT J. , MITROVIĆ K. , MOSTARICA M.
Published: June 2006

Rabbit anti‐rat brain synaptic membrane and anti‐rat thymocyte antisera were used in cytotoxicity, immunofluorescence, and absorption assays to define the antigenic relationship between the rat brain and thymocytes, and the localizing properties of antibodies. Both antisera cross‐reacted with brain tissue and thymocytes. However, anti‐synaptic membrane and anti‐thymocyte antisera also contained antibodies specific for neurons and thymocytes, respectively, Immunofluorescence showed that antibodies from anti‐thymocyte antiserum reacted with antigenic determinants situated on the surface membrane of brain cells.
Subpopulations of Cells Involved in the Human Mixed Lymphocyte Culture Response
Authors: BLOMGREN H.
Published: June 2006

Various subpopulations of human peripheral lymphoid cells were tested for their role in the mixed lymphocyte culture (MLC) response. Preparations of lymphocytes enriched for T cells, separated by a rosette sedimentation technique, were usually found to exhibit higher MLC responses than preparation enriched for B cells. The relatively high responses of B‐cell‐enriched preparations could largely be explained by contaminating T cells (approximately 5%) whose MLC reactivities were strongly enhanced by autologous non‐T lymphocytes. Cell preparations enriched for B cells were found to be more potent stimulators of MLC responses than T‐cell‐enriched preparations in most responder‐stimulator cell combinations. An MLC response could only be elicited in the presence of cells with characteristics of monocytes/macrophages. These cells could be derived from cither the responder or the stimulator.
Ultrastructure of Effector–Target Cell Interaction in Secondary Cell‐Mediated Lympholysis
Authors: BARBER T. A. , ALTER B. J.
Published: June 2006

The ultrastructure of the secondary cell‐mediated lympholysis (CML) reaction and the effects on interacting lymphocytes of colchicine, cytochalasin B, and effector cell‐Specific antisera were examined using transmission and scanning electron microscopy. Surface labelling of cytotoxic secondary effector cells with cationized ferritin allowed them to be distinguished from unlabelled target lymphocytes. Effector target interactions were characterized by intercellular junctions involving extensive areas of membrane opposition and interdigitation and extension of pseudopod‐like processes by the effector cell. The abolition of such interactions when effector populations were pretreated with anti‐Ly2 sera plus complement demonstrated target cell destruction in secondary CML to be dependent on the activity of restimulated cytotoxic T lymphocytes. Cytochalasin B and colchicine dramatically decreased the numbers of Specific effector‐target cell interactions observed. Although the data presented do not allow the possible activity of soluble lytic factors associated with the effector cell surface to be ruled out, they suggest that target cell lysis in the secondary CML system examined results From immune‐specific binding of alloantigen‐sensitized effectors to targets and osmotic effects which follow localized disruption of the target cell membrane.
B‐Cell Activating Properties of Polymyxin B
Authors: SMITH C. I. E. , HAMMARSTRÖM L.
Published: June 2006

Polymyxins are known to be inhibitors of certain polyclonal B cell activators such as lipopolysac‐charide and dextransulphate. However, increased specific responses to hapten‐coupled mitogens have been reported after the addition of polymyxins to superoptimal conjugate doses. In this paper we have studied the effect of polymyxin B on superoptimal polyclonal doses of lipoporysaccharide. Results similar to those reported for hapten‐lipopolysaccharide conjugates were obtained. Polymyxin B was also found to exert adjuvant properties for a primary immune response to sheep erythrocytes and to be a thymus‐independent antigen.
In Vitro Mitogen Stimulation of Synovial Fluid Lymphocytes from Rheumatoid Arthritis and Juvenile Rheumatoid Arthritis Patients: Dissociation between the Response to Antigens and Polyclonal Mitogens
Authors: ABRAHAMSEN T. G. , FRØLAND S. S. , NATVIG J. B.
Published: June 2006

The in vitro responses to mitogens of synovial fluid lymphocytes obtained from eight patients with rheumatoid arthritis (RA) and eight patients with juvenile rheumatoid arthritis (JRA) were studied. The results were compared to the transformation of the patient's peripheral blood lymphocytes stimulated with the same mitogens. Both RA and JRA synovial fluid lymphocytes showed a low transformation to the polyclonal mitogens PHA and PWM with a low ratio PHA‐response/PWM‐response. The stimulatory effect of purified protein derivative of tuberculin (PPD) was high, whereas a Candida albicans antigen preparation gave a more variable stimulation of the synovial fluid lymphocytes. In some patients the complete mitogen transformation profile of lymphocytes obtained from synovial fluid, synovial tissue and peripheral blood was studied. The results of the synovial fluid and tissue lymphocytes were similar.
Expression of VH Antibody Genes in Different Background Genomes
Authors: MÄKELÄ O. , KARJALAINEN K. , MICKLEM H. S.
Published: June 2006

We studied whether Ig‐1 linked Mendelian genes controlling antibody specificity usually express themselves independently of genes in other chromosomes (in particular, structural L chain genes = Vl genes). A VH gene VHNPb (controsl anti‐NP antibody can be demonstrated in most mouse strains with allotype b but not in Other strains, e.g. BALB/c and CBA. Our data show that BALB/c and CBA background gnomes permit expression of the VHNPb gene. We conclude that it expresses itself in at least five out of six background genomes tested (C57BL, LP, 101, CBA, BALB/c). Strain SJL may either lack the VHNPb gene or have a background genome that does not support its expression. Another VH, gene. VHABA‐HOPb, can be demonstrated in both of the two allotype b strains tested, but also in strains of other allotypes but not in CBA mice CBA(Ig‐1a). The congenic strain CBA‐Ig‐1b made anti‐ABA‐HOP antibody of the Ig‐1b type, again suggesting that VH genes find most background genomes suitable for expression. This is also suggested by the finding that a VH gene of the BALB/c strain (VHNBrPa1), which cannot be demonstrated in C57BL mice, expressed itself in a predominantly C57BL background. The two Ig‐1b strains 101 and CBA‐Ig‐1b had slightly different fine‐Specificities in their anti‐ABA‐HOP antibodies. The result suggests that in some cases the background genome has a minor, perhaps quantitative, effect on the expression of VH genes, but the basic conclusion remains that Mendelian polymorphisms can easily be demonstrated in the VH genes but not in the Vl, genes of the mouse.
Receptors for IgM on Human B Lymphocytes
Authors: PICHLER W. J. , KNAPP W.
Published: June 2006

Using a rosette technique with IgM coated bovine red blood cells (EA‐IgM) receptors for IgM can be demonstrated on human B‐lymphocytes. While in the peripheral blood B cells with IgM receptors are found only occasionally, between 7 and 33%, mean 16%, of tonsil B‐lymphocytes exhibit receptors for IgM. This was shown in double marker studies using EA‐IgM for the demonstration of IgM receptors and fluorochrome labelled conjugates for the demonstration of S‐IgD, S‐IgM and B cell antigens. These receptors are specific for IgM, they can be completely blocked by IgM‐anti OVA complexes and partially by free IgM, but not at all by aggregated human IgG. They are sensitive to trypsin and pronase but reconstitute after further incubation at 37°C. These data show that not only T and CLL cells but also some normal B‐lymphocytes have receptors for IgM. We favour the view that CLL lymphocytes may derive from these B‐lymphocytes, which may represent a certain maturation step in B cell development.
Role of Suppressor T Cells in Autoimmune Responses Induced by Polyclonal B Cell Activators
Authors: PRIMI D. , SMITH C. I. E. , HAMMARSTRÖM L.
Published: June 2006

In order to investigate a possible role of suppressor T cells in the maintenance of self tolerance, we compared the autoimmune response induced by LPS in cultures of untreated spleen cells with the one of anti‐theta treated spleen lymphocytes. It was constantly found that T cell depletion never resulted in an increase in the number of plaques directed against autologous albumin coupled SRBC. The same finding was also apparent when the autoimmune response given by spleen cells of old, normal or thymectomized and young untreated animals was compared. In order to exclude the possibility that lack of increase of the autoimmune response in animals with T cells deficiency was due to long‐lived suppressor functions, cells or factors, we compared the response to autologous albumin, as induced by LPS, in spleen cells of nude mice with the one given by their normal littermates. Since even in this instance no significant increase could be detected, we conclude that suppressor cells do not play an active role in the maintenance of self tolerance.
Certain Rheumatoid Factors React with both IgG and an Antigen Associated with Cell Nuclei
Authors: HANNESTAD K.
Published: June 2006

Rheumatoid factors (RF) were isolated by their affinity for human IgG. RF from three out or twenty‐four sera (12%) with a RF‐latex titre 20 and an anti‐nuclear antibody (ANA) titre 250 cross‐reacted with nuclei from mouse cells. This antibody which represents an unknown proportion of RF, is designated RF/ANA. Only one of the three sera (Nil) contained large amounts of RF/ANA. A fourth scrum (Jos) had 6.6 mg of RF per ml and an ANA‐titre of 4096; all the ANA‐activity of this serum was absorbed by an IgG–agarose conjugate. Pan of the RF‐activity of serum Jos was carried by antigenically deficient IgM. The ANA‐activity of purified RF/ANA from four sera was inhibited by low concentrations of aggregated human IgG and by higher concentrations of human Fcγ fragments and non‐aggreated mouse anti‐DNP anybodies. The data provide strong support for the conclusion that certain antibody molecules can combine with both IgG and an antigen in cell nuclei.
Effect of Membrane Stabilizing Agents on Induction of the Immune Response
Authors: SMITH C. I. E. , HAMMARSTRÖM L. L. G. , WATERFIELD J. D.
Published: June 2006

The effect of three membrane stabilizing compounds, chlorpromazine, imipramine and lidocaine, on mouse spleen cells was investigated. Cellular activation by the B‐cell mitogen lipopolysaccharide (LPS) was found to be inhibited. Suppressing doses also inhibited background DNA‐synthesis and the number of background plaque forming cells. However, the degree of suppression caused by all three of the membrane stabilizing agents tested, parallelled the decline of viable cells in the cultures. It is concluded that the drug induced inhibition of LPS activation was due solely to the toxicity of the compounds.
A Solid Phase Enzyme‐linked Immunosorbent Assay (ELISA) for the Demonstration of Antibodies against Denatured, Single‐stranded DNA in Patient Sera
Authors: GRIPENBERG M , LINDER E. , KURKI P. , ENGVALL E.
Published: June 2006

A solid phase enzyme‐linked‐immunosorbent assay (ELISA) for the determination of antibodies against denatured, single‐stranded (ss‐) DNA is described. Polystyrene cuvettes coated with ss‐DNA were incubated with serum samples and the anti‐ss‐DNA antibodies bound were detected by means of an anti‐IgG‐alkaline phosphatase conjugate. The binding of anti‐ss‐DNA antibodies in individual sera was expressed as units calculated as % of the absorbance in relation to the absorbance value obtained with a reference pool. Absorption experiments showed that the assay is specific for antibodies against denatured DNA. By using immunologically purified anti‐ss‐DNA antibodies the assay was shown Co detect specific antibodies in concentrations down to 1 ng/ml. Antibodies against DNA could be detected in 94% of sera with antinuclear antibodies.
Reversible Changes in Cytolytic T Lymphocyte Function Induced by Hyperthermia
Authors: MacDONALD H. R. , McFARLANE D. L.
Published: June 2006

The ability of cytolytic T lymphocytes (CTL) generated in vitro in mixed leucocyte cultures (MLC) to ‘repair’ functional damage induced by moderate hyperthermia has been investigated. Repair of CTL function was assessed in a split dose system in which MLC cells were exposed to a total of 20 min at 43°C delivered either as a single treatment or as two 10 min fractions separated by an interval at 37°C. Significant repair was observed within 15 min at 37°C in the split‐dose protocol and maximum repair (corresponding to a 30‐100‐fold increase in lytic activity) was seen after 1.5‐2 h. Repair was both temperature and energy dependent and was apparently related to a reversible lesion in the cytolytic mechanism itself. The effect of a number of metabolic inhibitors (and other agents) on repair was determined, but the precise nature of the heat‐induced lesion could not be identified.
Platelet Activation: a New Biological Activity of Guinea‐pig C3a Anaphylatoxin
Authors: BECKER S. , MEUER S. , HADDING U. , BITTER‐SUERMANN D.
Published: June 2006

3H‐serotonin‐release from labelled gp‐platelets is established as a sensitive method for testing a new biological activity of gp‐C3a anaphylatoxin in an autologous situation. Time‐, dose‐ and temperature‐dependent release reactions as well as specific inhibition by carboxypeptidase Band anti‐C3a antibodies show that C3a is a potent and specific inducer of platelet activation. Inactive C3a does not induce 3H‐serotonin‐release but specifically inhibits the action of C3a on platelets.