HLA-DR-specific suppressor cells after repeated allogeneic sensitizations of human lymphocytes in vitro.

In conclusion, DR-specific suppressor cells can be induced by repeated in vitro sensitizations. They were able (1) to decrease a secondary proliferation, (2) to suppress consistently, in a primary proliferative assay, when added as third cells (primed twice against a DR antigen [PLT II] and gamma-irradiated), the response of unprimed cells towards stimulating cells, which share a DR specificity with the priming cell of the PLT II. The suppression follows the D part of the recombinant haplotype within an HLA-B/D recombinant family and is specific for the DR antigen used twice as stimulator for production of the PLT II.     

HLA and non-HLA phenotyping and genotyping in Austral and Gambier Polynesian Archipelagos

Forty-one individuals from Rurutu Island (Austral Archipelagos) and 41 individuals from the Gambier Archipelagos have been typed for HLA; for blood groups ABO, Rh, MNSs, P, Kell, Kp, Lewis, Lutheran, Kidd; for the electrophoretic systems G6PD, 6-PGD, PGM1, PGM2, AcP, ADA, GPT, Est-D, GLO I, and for the immunoglobulin allotypes Gm and Km. There is a high degree of homogeneity among these Polynesian populations and among other Polynesian populations previously typed. However, small differences exist between the populations of the two archipelagos, possibly due to endogamy or to the smallness of the samples studied. A variant of HLA-Bw22 (called Bw22x) is described.     

Erythrocytes in human transplantation: effects of pretreatment with ABO group-specific antigens

Erythrocyte group antigens A and B can act as potent and group-specific transplantation antigens in man. ABO group-incompatible recipients pretreated with such antigens have rejected skin allografts obtained from donors incompatible for the same antigens in an accelerated (4-5 days) or white graft manner. Skin grafts applied to the same recipients from ABO-compatible donors were accorded first-set survival times. Intact erythrocyte suspensions and antigens isolated from hog (A substance) and horse (B substance) stomachs, were equally capable of inducing this type of allograft sensitivity. The latter observation broadens the spectrum of heterologous antigens capable of inducing allograft sensitivity in the mammalian host and provides a readily available, heat-stable, and water-soluble source of antigens for further studies of allograft rejection mechanisms in man.     

Presence of SLA and Ia-like antigen on boar spermatozoa.

Several parameters for serological tests on boar spermatozoa were studied, and a reliable technique was developed and employed. Using SLA (the MHC system in pig) genotyped boars, and specific reagents, SLA and Ia-like antigens were demonstrated on the sperm using both the cytotoxic and the absorption test. No SLA activity was detected in the seminal fluid.     

PRESENCE OF SLA AND Ia-LIKE ANTIGEN ON BOAR SPERMATOZOA

Several parameters for serological tests on boar spermatozoa were studied, and a reliable technique was developed and employed. Using SLA (the MHC system in pig) genotyped boars, and specific reagents, SLA and Ia-like antigens were demonstrated on the sperm using both the cytotoxic and the absorption test. No SLA activity was detected in the seminal fluid.     

A linkage disequilibrium map of the MHC region based on the analysis of 14 loci haplotypes in 50 French families

A sample of 100 individuals from 50 French families of known pedigrees were typed for 14 loci of the HLA region (DPB1, DQB1, DQA1, DRB1, DRB3, 4, 5, C4B, C4A, Bf, C2, TNFa, TNFb, B, Cw, A). Linkage disequilibrium in each pair of loci was investigated by an exact test using a Markov chain algorithm. The results indicate no disequilibrium between DPB1 and the other loci, whereas the other class II genes are all significantly linked to each other. Linkage disequilibrium is also detected between some pairs of class I and class II-class I loci despite the long physical distance separating the loci (e.g. A-B, Cw-DRB1). On the other hand, some contiguous loci of the class III region are found to be in equilibrium with each other. Several hypotheses including selection, but also unequal allelic diversity at different MHC loci are discussed to explain this complex pattern of linkage disequilibrium.     

Behavioral alterations associated with apoptosis and down-regulation of presenilin 1 in the brains of p53-deficient mice

Presenilin 1 (PS1) expression is repressed by the p53 tumor suppressor. As shown herein, wild-type PS1 is an effective antiapoptotic molecule capable of significantly inhibiting p53-dependent and p53-independent cell death. We analyzed, at the functional and molecular levels, the brains of p53 knockout mice. Surprisingly, we found that lack of p53 expression induces apoptotic brain lesions, accompanied by learning deficiency and behavioral alterations. p53-deficient mice show an unexpected overexpression of p21(waf1) with subsequent down-regulation of PS1 in their brains. This process is progressive and age-dependent. These data indicate that the p53 pathway, besides affecting tumor suppression, may play a major role in regulating neurobehavioral function and cell survival in the brain.     

Linkage proof for PTPN22, a rheumatoid arthritis susceptibility gene and a human autoimmunity gene

The tyrosine phosphatase PTPN22 allele 1858T has been associated with rheumatoid arthritis (RA) and other autoimmune diseases. RA is the most frequent of those multifactorial diseases. The RA association was usually restricted to serum rheumatoid factor positive disease (RF+). No interaction was shown with HLA-DRB1, the first RA gene. Many case-control studies replicated the RA association, showing an allele frequency increase of approximately 5% on average and large variations of population allele frequencies (2.1-15.5%). In multifactorial diseases, the final proof for a new susceptibility allele is provided by departure from Mendel's law (50% transmission from heterozygous parents). For PTPN22-1858T allele, convincing linkage proof was available only for type 1 diabetes. We aimed at providing this proof for RA. We analyzed 1,395 West European Caucasian individuals from 465 "trio" families. We replicated evidence for linkage, demonstrating departure from Mendel's law in this subset of early RA onset patients. We estimated the overtransmission of the 1858T allele in RF+ families: T = 63%, P < 0.0007. The 1858T allele frequency increased from 11.0% in controls to 17.4% in RF+ RA for the French Caucasian population and the susceptibility genotype (1858T/T or T/C) from 20.2% to 31.6% [odds ratio (OR) = 1.8 (1.2-2.8)]. In conclusion, we provided the linkage proof for the PTPN22-1858T allele and RF+ RA. With diabetes and RA, PTPN22 is therefore a "linkage-proven" autoimmunity gene. PTPN22 accounting for approximately 1% of the RA familial aggregation, many new genes could be expected that are as many leads to definitive therapy for autoimmune diseases.