Are HLA and Chido related antigenic groups?
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Biomedical subjects
Publications and source records attributed to R A Good.
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Human B-lymphocyte differentiation was studied by measuring the capacity of such cells, isolated from peripheral blood, to synthesize and secrete Ig after pokeweed stimulation. Results show that a maximum incorporation of [3H]-thymidine took place 2 days before the appearance of detectable Ig-secreting cells. On the 7th day after pokeweed stimulation, when Ig synthesis and secretion are at a maximum, [3H]-thymidine uptake was low. Since inhibition of DNA synthesis 3 days after pokeweed stimulation completely prevents the generation of Ig-secreting plasma cells, initial DNA synthesis is apparently essential before Ig-secreting plasma cells can develop in response to pokeweed stimulation.
The effect of anti-immunoglobulin (anti-Ig) on cultures of established human B-cell lines was studied to develop models for the initiation and regulation of immune responses. DNA synthesis in one line, BM, measured by [125I]iododeoxyuridine (IUdR) incorporation, was stimulated by anti-Ig when the continuously proliferating cultures approached high cell density. One of four lines, BJAB, was very sensitive to inhibition of DNA synthesis by anti-Ig at all cell concentrations. Of four human T-cell lines tested for suppressor activity, the CEM line was found to be activated by concanavalin A (Con A) to inhibit the anti-Ig stimulation of BM cells. No cytotoxic activity was detected in Con A-treated CEM cells. Both the anti-Ig stimulation of BM and Con A-induced suppression by CEM occurred with cloned cell lines in long-term culture, in the absence of helper or accessory cells.
T lymphocytes with receptors for IgM(Tmu) and IgG(Tgamma) were examined in thirty patients with primary immunodeficiency and autoimmune disorders. Six out of twenty-seven patients with primary immunodeficiency had a low proportion of Tmu cells when compared with normal controls. Eight out of twenty-seven patients with primary immunodeficiency had an increased proportion of Tgamma cells. Two out of twenty-seven patients had both a low proportion of Tmu cells and a high proportion of Tgamma cells. The patient studied with severe combined immunodeficiency had a low proportion of both Tmu and Tgamma cells. Patients with Bruton-type agammaglobulinaemia, common variable immunodeficiency, thymoma and immunodeficiency syndrome and selective IgA deficiency demonstrated heterogeneity with regard to alterations in T-cell subpopulations.
Human gastrointestinal cancer xenografts were established in the nude mouse. Grafts were accomplished with gastric adenocarcinomas, gastric leiomyosarcoma, histiocytic lymphoma of the stomach and gallbladder, pancreatic tumors, colonic cancers and cell lines of duodenal (HUTU-80) and pancreatic (HS-766-T) cancers, melanoma (SK-Mel-5), and murine metastasizing Lewis lung carcinoma. The rate of successful xenografting of these tumors varied from virtually 100% with colon and duodenal cancer, 50% for a pancreatic cancer (P-1), to only 17% for gastric adenocarcinoma. Pancreas and colon adenocarcinomas have been maintained by successive xenotransplantation over 16 and 19 months, respectively. Human xenografts retained morphological identity with tissues of origin through several transplant generations and shared some of their ultrastructural characteristics but did not metastasize. Rodent xenografts, of heterogenous origin were characterized by differences in the duration of the latent period and in the rate of their initial development as described by the average doubling times and average slopes (B) of their growth curves. Differences between B of the Lewis lung carcinoma and all of the human xenografts and between B of a pancreatic adenocarcinoma and three other neoplasms were significant (P less than 0.05 to 0.04). Labeling indices determined for 14 cancer transplants were in the range of previously reported data for similar neoplasms in patients or other xenograft systems. These findings suggest that the nude mouse model can be used to evaluate endogenous properties of gastrointestinal cancers and their responses to exogenous agents.
Twenty consecutive patients with Hodgkin disease in continuous complete remission and off treatment for at least 5 yr (range 5-25 yr, median 9 yr) were studied with a battery of immunologic parameters. Skin test reactivity to four common antigens, sensitization to 2,4-dinitrochlorobenzene, absolute lymphocyte count, relative percentage of T cells (as measured by spontaneous rosette formation with sheep erythrocytes) and B cells (as measured by immunofluorescence with polyvalent antiserum), and absolute number of T and B cells were normal when compared with controls. However, the mean value of lymphocyte response in vitro to the mitogen phytohemagglutinin for the study population was significantly decreased (p less than 0.001) when compared with the controls. This abnormality in response to mitogen could not be correlated with age, sex, stage, symptoms, histologic subclassification, or previous treatment. The data suggest the existence of a persisting cell-mediated immune defect in the circulating lymphocytes in patients with long-standing Hodgkin disease that might otherwise be considered "cured."
Leukemic cells from nine cases of acute monocytic leukemia (AMoL) were characterized by multiple differentiation markers. Cells in most cases were phagocytic, carried an Fc receptor, and stained positively for alpha-naphthyl acetate esterase but negatively for naphthol AS-D chloroacetate esterase. However, subtle differences in marker expression were observed which suggested different degrees of leukemic cellular maturation or activation. Cell marker analysis proved to be a useful adjunct to conventional morphology in confirming the diagnosis and the recognition of the neoplastic cells in AMoL, and may ultimately provide insight into the functional state of these cells.
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Mononuclear cells from twenty human tonsils and peripheral blood lymphocytes were examined for T, B and 'third population cells'. Compared with peripheral blood lymphocytes, tonsils were found to have a higher proportion of B lymphocytes with surface IgM, IgD and IgA. Mouse erythrocyte rosette-forming cells were also present in increased proportions. However, 'third population cells' were found in very low proportions. Phagocytic cells as determined by latex ingestion and peroxidase staining were also present in low proportions. The lack of 'third population cells' in human tonsils may establish this organ as one of particular interest in the study of lymphocyte subpopulations because T and B lymphocytes can be purified without contaminating 'third population cells'. The role of the third population of lymphocytes in antibody-dependent cytotoxicity and spontaneous cytotoxicity may be supported by the absence of these functions along with absence of the 'third population' cells from tonsilar lymphoid cells.
The study of human lymphoid cell differentiation markers has recently yielded many insights into the pathogenesis of certain diseases which primarily affect the immune system. The application of these markers has, however, generated a host of new questions. Both technical difficulties and uncertainties concerning the significance of particular markers limit their routine application at the present time. Indeed, many studies in the literature, both in the diseases reviewed above, and perhaps to a greater degree in other conditions ('autoimmune' diseases, sarcoidosis, hepatitis and various infections) require re-evaluation in the light of recently increased sophistication about cell surfaces. Because of these qualificatins, the application of multiple characterizations of lymphoid cells using independent methodologies is necessary before any firm conclusions can be drawn in a particular clinical or experimental situation.
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Peripheral blood lymphocytes were incubated with varying concentrations of alpha-fetoprotein and enumerated for total and ""active'' T lymphocytes, B lymphocytes, and their proliferative responses to phytohemagglutinin. No significant effect was observed on total T or B lymphocyte proportions. However, there was a dose-related increase in proportions of the so called "active" T lymphocytes. The response of human lymphocytes to phytohemagglutinin was markedly depressed. The alteration in the proportion of active T cells and the inhibition of T lymphocyte response to phyto hemagglutinin by alpha-fetoprotein occurred at higher concentrations than are present in amniotic fluid, serum of pregnant women, or serum of adults, but well within the range reached in fetal serum. The immunoregulatory role of alpha-fetoprotein is discussed.
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Basal cell carcinoma (BCC) is the most common form of skin cancer, accounting for 65% to 75% of all malignant skin tumors. Metastic BCC is very rare--only 109 documented cases have been reported to date. The mean time of survival after metastasis has been reported to be ten months. No effective therapeutic modality is known for its treatment. We are reporting a case of metastatic BCC in which we have found deficiency of cell-mediated immunity. Postmortem studies showed a co-existing squamous cell carcinoma in thelungs, brain, liver, and spleen. The most unusual finding in the postmortem study was evidence of juxtaposition of BCC and epidermoid carcinoma with distinct histologic dimorphism. We speculate that a combination of immunodeficiency and stromal independence is needed for metastases in BCC.
Congenital neutropenia (CN), a disease characterized by recurrent infections leading to death in infancy, shows a maturation arrest of the myeloid series at the promyelocyte-myelocyte level. The potential value of marrow transplantation in this disease would be determined by the nature of the underlying defect. However, studies to date have failed to define whether the defect is intrinsic in the cells or attributable to "environmental" factors. Therefore, marrow of four patients with CN was cultured on soft agar, and the colonies were analyzed by a newly developed ultrastructural method. In parallel, patients' cells were used in feeder layers for normal marrow. Although the patients' colonies appeared grossly normal in size and number, electron microscopy showed only rare neutrophil colonies. These colonies contained markedly aberrant cells exhibiting asynchronous nucleocytoplasmic maturation, convoluted nuclei, excessive cytoplasm, and dearth of granules. Monocyte and eosinophil colonies differentiated normally. Patients' cells and sera supported growth of normal colonies. The studies have demonstrated unequivocally that the neutrophil cell line of patients with CN is intrinsically defective and suggest that attempts at marrow grafting are warranted.
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