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Biomedical subjects

F Kissmeyer-Nielsen

Publications and source records attributed to F Kissmeyer-Nielsen.

At least 73 records · Page 4Linked to original sources

Cell mediated lympholysis in man: an attempt to type with cytotoxic lymphocytes.

From approximately 3,000 CML combinations, originally established in order to evaluate the qualitative and quantitative influence of the serologically defined HLA-A, B, and C antigens on cellular, complement independent cytolysis, 12 combinations were selected yielding reproducible positive cytolysis on allogenic target cells, although no HLA-antigenic sharing could be demonstrated between stimulator and target lymphocytes. These 12 CytoToxic Lymphocytes (CTL's) have been tested in parallell as "CML typing combinations" against lymphocytes from a random population sample of 100 unrelated Danes. Based on a pairwise analysis 11 of these CTL's could be classified into two groups of significantly correlated CTL's. These two groups do not define monospecific traits of allelic genetic origin as judged by a mutually positive correlation and a poor fit to Hardy-Weinberg equilibrium. The traits defined by these groups may be either partially identical or governed by closely linked loci. The same groups were identified and the same conclusions reached after exclusion of those individuals in the population sample where HLA-A, B, C, or D antigens may be targets for destruction. Thus, this study gives direct evidence that known HLA antigens are not sole target determinants in CML or that cytotoxic lymphocytes recognize HLA molecules in a different way than lymphocytotoxic antibodies. The studies underline the immunogenetic complexity of CML although this reaction is most probably governed by genes in the HLA region. It is suggested that cytotoxic lymphocytes may recognize "backbone structures" of the HLA molecules.

Cytotoxicity Tests, Immunologic↗

Cell mediated lympholysis in man. The impact of HLA-C antigens.

From a population of individuals, all HLA-A, B, and C tissue typed in relation to the Sixth International Histocompatibility Workshop, an experimental investigation has been performed to study the influence of the HLA-Cwl, w2, w3, w4, and w5 antigens in the Cell Mediated Lympholysis (CML) test. The average cytolysis obtained due to allogenic attack of one HLA-C antigen equals 12.6%, but like the HLA-A and B antigens, HLA-C antigens exhibit differences with regard to sensitizing and target potential. This indicates either a heterogeneity of these antigens or the existence of separate CML determinants. It is concluded that the HLA-C antigens may account for the cytolysis observed in some of the combinations exhibiting cytolysis which cannot be explained by the HLA-A and B antigens.

Epitopes↗

Hyperacute rejection of a kidney allograft may be caused by cytotoxic lymphocytes.

A case of hyperacute rejection of a kidney allograft is described in relation to the clinical, patho-anatomical, and immunological findings. An 18-year-old male was allotransplanted for the third time with a necrokidney from an unrelated HLA-A and B, full house identical and blood group ABO identical donor. Serological crossmatches performed with recipient sera harvested before and after transplantation were negative. In spite of this, the kidney suffered hyperacute rejection according to clinical and patho-anatomical criteria. The cellular, complement independent cytolytic capacity of recipient lymphocytes drawn before and after transplantation against donor lymphocytes was tested by the direct Cell Mediated Lympholysis (CML) test. This test was positive 24 hours after transplantation, whereas it had been negative before this. Lymphocytolysis was enhanced by inactivated recipient serum harvested before and after transplantation. These findings suggest that hyperacute rejection of a kidney allograft may be ascribed to presensitized, not necessarily circulating, effector lymphocytes either alone, or in concert with antibody(ies) not disclosed by conventional crossmatching.

Acute Disease↗

Occurrence of lymphocytotoxic lymphocytes and antibodies after corneal transplantation.

Twentyfive recipients of penetrating corneal grafts were investigated for the presence in the peripheral blood of cytotoxic lymphocytes by the Direct Cell Mediated Lympholysis (Direct CML) test as well as for lymphocytotoxic antibodies. Eight patients presented a positive Direct CML. Six of these patients have shown clinical signs of graft rejection, while two patients had a clinically uncomplicated course. Only one of the 25 patients had lymphocytotoxic antibodies. This patient showed a negative Direct CML, and a clinically uncomplicated course.. The findings seem to imply that recipients of corneal grafts can be immunized by their grafts and that cytotoxic lymphocytes in peripheral blood appear frequently in those patients showing graft rejection.

Adult↗

Rga (Rodgers) and the HLA region: linkage and associations.

In 19 families with 97 children the segregation of Rga (Rodgers) was found to be compatible with Mendelian inheritance and five backcross and 14 intercross families were found among HLA and Bf typed families. Close linkage (lods + 17.82) without recombination was found between Rg and the HLA region, with a direct count of 96 nonrecombinant meioses for Rg-HLA-B. Rg- was strongly associated with HLA-B8 (29 of 30 haplotypes) and probably associated with Bw40, but did occur on other HLA-B haplotypes. By inference Rg- is negatively associated with Ch- (Chido). The Rg-Ch- haplotype has not been observed. Rga and Cha may or may not be coded for by different sites of the same cistron closely linked to HLA-B:C and cannot as yet be excluded from being parts of B or C.

Blood Group Antigens↗

Cell mediated lympholysis in man. Patterns of killing power in relation to the HL-A system.

In general it can be said that the HL-A (LA and FOUR) antigens seem to be of major qualitative and partly quantitative importance for the degree of destruction in Cell Mediated Lympholysis (CML). This has been established by analyses of 1299 effector/target combinations involving 97 different healthy individuals. The main observation is that the cytolytic capacity of MLC effectors is positively ranked with the number of HL-A (LA and FOUR) antigens introduced by the incompatibility between stimulator, effector and target lymphocytes. However, the fact that not all cytolytic situations can be explained by the HL-A system stresses that other specific antigens (Target Determinants) may interfere with the Cell Mediated Lympholysis.

Antigen-Antibody Reactions↗

Cell mediated lympholysis in man. Varying strength of the HL-A (LA and FOUR) antigens as sensitizing or target determinants.

The gene products of the LA and FOUR loci of the human Major Histocompatibility Complex (MHC) are generally considered to be a major target in the Indirect Cell Mediated Lympholysis (ICML) test. Within most experiments, a positive correlation exists between the number of HL-A antigens challenged and lympholysis. When different experiments are collated this correlation is less obvious. This discrepancy might be caused by differences between the individual HL-A antigens involved in the afferent phase (MLC) and/or the efferent phase (CML). In 28 experiments involving 97 unrelated individuals we have compared statistically 12 different antigens governed by the LA and FOUR loci. When only one of these antigens is challenged in ICML, target lymphocytes are lysed to different degrees allowing a significant classification of the antigens into different groups, which do not coincide with the classification in the LA and FOUR series antigens. It is concluded that the antigens of the HL-A system are not of equal importance when challenged separately in ICML. The existence of a separate CML locus and a corresponding linkage disequilibrium to the SD loci of the MHC region is suggested.

Antigen-Antibody Reactions↗

Cell mediated lympholysis in man. The HL-A third locus antigen, AJ (W20) as sensitizing and/or target determinant.

The Indirect Cell Mediated Lympholysis (ICML) test has become a reliable in vitro tool in investigations of the immunogenetic background of the cellular immune response. It is well established that the antigens of the LA and FOUR loci of the human Major Histocompatibility Complex (MHC) or antigens governed by closely linked loci exhibiting a marked linkage disequilibrium are of major qualitative and quantitative importance in ICML. This communication is concerned with the importance of the HL-A third series antigen AJ (W20) on lympholysis in ICML. From investigations of 47 combinations where only the AJ (W20) antigen may be attacked, it is concluded that this antigen is, in itself, a poor ICML target determinant, but that AJ (W20) may function as a stronger ICML target determinant in concert with a FOUR antigen, although the actual FOUR antigen cannot be attacked.

Antigen-Antibody Reactions↗

MLC results among unrelated can be predicted.

Typing for LD determinants which has been practicable for some time is shown to be very predictive for the MLC response between unrelated, since LD identical individuals-selected and paired solely on the basis of LD typing-mutually show very low or no MLC reaction.

Female↗

Direct cell mediated lympholysis. A test of allograft-rejection in human kidney recipients.

In kidney transplanted patients a clear coincidence was observed between clinical signs of allograft rejection and the presence in the peripheral blood of killer cells able to lyse either PHA lymphoblasts from the actual donor or selected unrelated individuals. In recipients with non-immunological complications such as leakage on the graft ureter or primary anuria caused by renal ischaemia, no cellular cytotoxicity against specific or selected target cells was observed. The specificity of this Cell Mediated Lympholysis in two of the cases reported could not be explained by the serologically detectable HL-A antigens, indicating the existence of other determinants of importance for the killing capability of in vivo produced effector cells.

Adult↗

Data on the HL-A linkage group.

Lod scores from a study in 229 families of the linkage relations of HL-A-PGM3 to 19 marker loci and cystic fibrosis are reported. The data exclude that ADA belongs to this linkage group while they give weak support for the inclusion of P. There is weak evidence for linkage of cystic fibrosis to PGM3, but none for linkage to HL-A. No new suggestive linkages appeared.

Blood Group Antigens↗