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Immunological evaluation of 20 patients with retinitis pigmentosa (RP) revealed significantly diminished circulating T-lymphocyte numbers and function and a high frequency of serum antibodies to human IgG in comparison with a healthy matched control population. However, these differences were due to severely abnormal results found in one subpopulation within the total patient group; this dichotomy was unrelated to the mode of inheritance or clinical severity of RP in individual patients. Thus, RP appears to be a syndrome rather than a disease and includes a form characterized by defective immunity. Whether this is involved in the pathogenesis of the retinal degenerative process is conjectural.

A radioimmunoassay (RIA) for the determination of autoantibody on the surface of erythrocytes from New Zealand Black (NZB) mice is described. This method was adapted to hemagglutination plates in order to facilitate the separation of bound and unbound 125I-labeled rabbit anti-mouse immunoglobulin G with an automated cell harvester. Intra- and interday precision, over the useful quantitative range of the standard curve, was 3.9 and 12.9%, respectively. The RIA was five to ten times more sensitive than the direct antiglobulin test which, unlike the RIA, provided little quantitative information on a group of 20 experimental NZB mice. This is publication number 562 from the Department of Basic and Clinical Immunology and Microbiology, Medical University of South Carolina.

The effects of human osteosarcoma (OS)-specific dialyzable leukocyte extracts (DLE) in hamsters bearing human OS were investigated. The DLE used in this investigation was prepared from rabbits immunized with human osteosarcoma-associated antigens (DLE-OSAA). Tuberculin (DLE-PPD) and control DLE were prepared from rabbits injected with tuberculin or 0.85% NaCl (DLE-NaCl). DLE was administered subcutaneously into inbred hamsters (each injection contained DLE derived from 10(7) rabbit leukocytes). Four groups of animals were studied: group 1, amputation alone; group 2, amputation plus DLE-OSAA; group 3, amputation plus DLE-PPD; group 4, amputation plus DLE-NaCl. Of the DLE-OSAA-treated animals (group 2), 60% were still alive at 300 days postamputation; whereas in animals in groups 1, 3, and 4, all died within 90 days postamputation. In separate experiments, we found that 100% of the animals in groups 1, 3, and 4 developed pulmonary metastases within 30-60 days postamputation, whereas only 20% of the animals in group 2 developed metastases at the same time; indeed 40% of the DLE-OSAA-treated animals were free of metastases in 240-300 days postamputation. Both the leukocyte adherence inhibition assay (LAI) and lymphocyte DNA synthesis assay (LDS) were used to monitor the transfer of antigen-specific cell-mediated immunity in each group of tumor-bearing hamsters. All surviving hamsters in group 2 had high LAI and LDS activity. Our results suggest that DLE-OSAA is effective in preventing pulmonary metastases and death of OS-bearing hamsters (after amputation) as compared with amputation alone, amputation plus DLE-NaCl, and amputation plus DLE-PPD, and that its effect is via an antigen-specific mechanism.

PHA stimulation assay was the first in vitro method for evaluating the T-cell function, and this T-cell proliferative response has been routinely used to discriminate between normal subjects and patients with deficiency in cell-mediated immunity. However, [3H]thymidine incorporation into lymphocyte DNA can be studied by using additional in vitro assay methods since they measure different lymphocyte activation pathways. In the present study we selected three different tests to investigate the reliability of this single approach: PHA induced lymphocyte DNA synthesis; T lymphocyte DNA synthesis to anti-T3 monoclonal antibody (OKT3); autologous mixed lymphocyte reaction (AMLR). In addition, IL-2 receptor expression on the membrane of T-cell stimulated in AMLR both with PHA and anti-T3 was evaluated. This study was performed in various groups of subjects: normal young controls, aged healthy individuals, and patients with Alzheimer's disease (AD), Retinitis Pigmentosa (RP), and with cell-mediated immunodeficiency and clinical evidence of recurrent viral infections (ID). The data reported herein show heterogeneity of results in each group studied and demonstrate the necessity of employing more than one laboratory test for the routine evaluation of T-cell-mediated immunity.

Huntington's Disease (HD) is a degenerative neurological disorder with autosomal dominant transmission. Although immunological defect(s) have been postulated, no confirmed laboratory evidence for this exists. In the present study we observed activated T cells in the peripheral blood of HD patients (using 4F2 monoclonal antibody), whereas the percentage of T cells bearing T-cell activation markers such as HLA-DR and MLR4 antigens was normal. We then studied T cells of HD patients in some functional assays. Since it has been suggested that autologous mixed lymphocyte reaction (AMLR) includes several immune mechanisms in which distinct cell subsets interact and perform distinct regulatory functions, it is conceivable that the remarkable deficiency of AMLR herein observed in HD patients results from some abnormal immune regulation which may contribute to the pathology of this condition. Additional experiments demonstrated a defect of AMLR in three asymptomatic young sibs of HD patients, and coculture experiments between T cells of patients (as responders) and non-T cells of their sibs (as stimulators), and vice versa, produced no proliferative response. Subnormal responsiveness in allogeneic MLR was also observed. Normal or enhanced PHA-induced production of both IL-2 and IFN-gamma in vitro was detected. These experimental data suggest a cellular branch of the immune system in HD; however, they do not indicate if this defect is primary or secondary to the disease itself.