Rat thymocyte membrane fractions have been prepared which exhibit strain-specific primary mixed-lymphocyte reaction (MLR)-stimulating and Ia (RT1-B) antigenic properties. These preparations lack the antigenicity of classical, serologically-defined RT1-A (Ag-B) antigens, as defined by in vitro serologic assays. Furthermore, after immunization of allogeneic hosts, specific anti-Ia and MLR-blocking antibodies, but not anti-AgB, alloantibodies are elaborated. Thymidine suicide experiments show that the same clones respond to whole cells and the fragments made from those cells, and the response segregates appropriately in F2 progeny as a major histocompatibility complex (RT1)-linked phenomenon. Hence, it is possible to generate Ia-related allogeneic helper signals in primary, as well as secondary, in vitro responses, using subcellular membrane fragments that have restricted expression of RT1-B-, but not RT1-A-, encoded antigens.

Animals↗

PubMed1980

Role of humoral presenitization in human renal transplant rejection.

A prospective study of 31 cadaveric renal allograft recipients was performed to determine the significance of pretransplant presensitization undetected by the conventional microlymphocytotoxicity crossmatch. Donor-specific humoral presensitization revealed by the antibody-dependent cell-mediated cytotoxicity assay (ADCC) was associated with a high incidence of early graft rejection. Six-month graft survival was 20% in recipients with positive pretransplant ADCC and 75% in ADCC-negative recipients (P < 0.01). Among recipients highly presensitized to a random panel of HLA antigens, donor-specific humoral presensitization detected by chromium-51-release complement-dependent cytotoxicity (51Cr-CDC) was also highly correlated with accelerated rejection (P < 0.05). Pathologic study of the rejected allografts revealed antibody-mediated rejection vasculitis in all recipients. We conclude that humoral presensitization undetected by current conventional methods plays a cardinal role in early renal graft rejection and is a major factor responsible for low cadaveric renal transplant survival. This study suggests that use of the ADCC and 51Cr-CDC as routine adjunctive crossmatch procedures may contribute to improvement in renal transplant survival rates.

Antibody Formation↗

PubMed1980

Public B cell alloantigen determinants (Ia) and active enhancement of renal allografts in the rat.

Experimental renal transplantation in the rat model has established that immunity to certain donor B cell Ia antigenic determinants is associated with enhanced graft survival. Preimmunization of LEW hosts with BUF lymphoid cells produced significant prolongation (P < 0.005 by log rank analysis) of survival of renal allografts taken from a third-party (LEW X BN)F1. Serological analysis demonstrated that BN and BUF share and MHC-encoded public Ia specificity, expressed on B cells, which we have called Ia.15. Hyperimmune sera directed at this specificity are cytotoxic to 20 +/- 3% of lymph node cells, significantly inhibit the formation of EA rosettes by Fc receptor-bearing cells (EAI), and inhibit mixed lymphocyte reaction (MLR) by 50 to 60% when directed at the stimulator but not when directed at the responder strain cells. Study of a large number of hyperimmune sera raised between inbred rat strains, by EAI and complement-dependent cytotoxicity (CDC) versus B cells, has revealed broad patterns of cross-reactivity, suggesting that public Ia determinants are both complex and highly immunogenic. Immunity restricted to a public Ia antigen plays a role in allograft enhancement.

Animals↗

PubMed1980

Early-onset pauciarticular juvenile rheumatoid arthritis associated with human leukocyte antigen-DRw5, iritis, and antinuclear antibody.

Evidence has been sought for a genetically determined predisposition among children with juvenile rheumatoid arthritis (JRA) who are also at particular risk for the development of inflammatory eye disease.45 unrelated Caucasian patients (41 female) with early-onset pauciarticular JRA were human leukocyte antigen (HLA) types. 28 of the study group were found to be HLA-DRw5 compared with 16 of 84 controls (X(2), 24.3, P = <0.001). 9 patients were HLA-DRw8 compared with 4 of 84 controls (X(2), 7.51, P = <0.01). Iritis developed in 24 of the 45 children studied, 17 of whom were typed as HLA-DRw5 when compared to controls (X(2), 26.76, P = <0.001) and 6 with iritis typed as HLA-DRw8 (X(2), 9.10, P = <0.01). Antinuclear antibody was found in the serum of 17 of the 28 patients typing as HLA-DRw5 compared with 4 of the 17 who did not have this antigen (X(2), 5.88, P = <0.02). No such association was seen in patients with HLA-DRw8. In a study of linked genes, a delta value of 0.090 was found for HLA-DRw5 with HLA-B12, of 0.070 for DRw5 with HLA-Cw4, and a value of 0.050 for DRw5 and HLA-Bw35. This suggests a linkage disequilibrium between HLA-DRw5 and these two B series alleles, a conclusion which was supported by haplotype analysis in families of 11 of the disease probands. HLA-DRw5 has not previously been reported to be increased in any rheumatic disease group. It is proposed that HLA-DRw5 is a genetic marker defining those at risk for early-onset pauciarticular JRA with iritis.

Antibodies, Antinuclear↗

PubMed1980

Cyclic nucleotides in immunosuppression--neuroendocrine pharmacologic manipulation and in vivo immunoregulation of immunity acting via second messenger systems.

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Animals↗