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Biomedical subjects

N Talal

Publications and source records attributed to N Talal.

At least 271 records · Page 15Linked to original sources

Functional deficiency of splenic adherent cells in New Zealand black mice.

New Zealand Black (NZB) mice hyporespond after in vitro immunization to sheep erythrocytes but not after in vivo immunization. The difference between in vitro and in vivo immunization was found to involve a non-antigen-specific change in the spleen which occurs in vivo soon after priming. Adherent spleen cells from young NZB or control strain mice were compared in their ability to cooperate with nonadherent cells in the induction of a primary immune response to sheep erythrocytes in vitro. The results support the hypothesis that there is a functional deficiency of adherent cells in the spleens of unprimed NZB mice.

Animals↗

Reversible restoration by thymosin of antigen-induced depression of spleen DNA synthesis in NZB mice.

Antigen-induced depression of spleen DNA synthesis was studied in NZB and CBA/J mice. This phenomenon, a measure of T suppressor cell activity, normally decreases as a consequence of aging. However, NZB mice have an accelerated loss of antigen-induced depression that can be restored by treatment with thymosin or injection of 1-month-old NZB thymocytes. The restoration by thymosin declined between 1 and 2 weeks after treatment, but could be induced again after a second exposure to thymosin. These results suggest a potential for reversible but repeatable restoration of suppressor cell activity in NZB mice.

Aging↗

Antibodies to nucleic acids in human and murine lupus.

Antibodies to nucleic acid are present in the sera of patients with systemic lupus erythematosus and in the sera of NZB/NZW F1 mice, an animal model for human systemic lupus erythematosus. Sera can be fractionated by sucrose-density gradient ultra-centrifugation and individual fractions assayed for binding of radioactive DNA, RNA or DNA: RNA hydridsive DNA, RNA or DNA: RNA hybrids. Immunoglobulin determinations can also be performed on these fractions. Antinucleic acid antibody activity can be recovered both in the 19S IgM and 7S IgG fractions. Individual variations from patient to patient suggest that more detailed analysis of immunoglobulin classes may provide insights into the pathogenesis of lupus.

Animals↗

Acceleration of autoimmunity in NZB/NZW F1 mice by graft-versus-host disease.

Chronic graft-versus-host (GVH) disease was induced in NZB/NZW F1 (B/W) hybrid female mice by the weekly injection of parental NZB spleen cells. Control mice received injections of syngeneic spleen cells only. The mice were assayed for antibodies to [3H]DNA and [3H]polyadenylic-polyuridylic acid by a cellulose ester filter radioimmunoassay, and for antibody to thymocytes by a cytotoxicity method. GVH disease accelerated the development of all three antibodies in B/W mice. In addition, sucrose density gradient ultracentrifugation of pooled sera suggested that an accelerated switch from 19S to 7S anti-DNA production may be an early effect of GVH. The mechanism of acceleration is discussed in terms of immunological and viral factors generated by the GVH reaction.

Animals↗

An unusual mouse myeloma protein binding native DNA.

SP 104 is an IgA-kappa myeloma protein produced by a lymphoid tumour of CA F1 mice. It arose originally in mice injected intraperitoneally with cell-free extract of spleen from a dog with systemic lupus erythematosus. The monoclonal nature of the IgA was shown by characteristic appearance on immunoelectrophoresis, restriction to a single light chain type and ability to induce anti-idiotypic antiserum. This protein has antibody activity against native (double-stranded) DNA and its specificity is similar to the antibodies against DNA found in the sera of humans with SLE and NZB/NZW F1 mice. Its idiotype does not cross-react with idiotypes of other mouse myeloma proteins known to bind DNA.

Animals↗

Protective and cellular immune responses to idiotypic determinants on cells from a spontaneous lymphoma of NZB-NZW F1 mice.

A spontaneous lymphoma (141) producing monoclonal IgM is established in NZB/NZW F(1) (B/W) mice who spontaneously develop an autoimmune disease. Idiotypic determinants of 141 IgM are present on the lymphoma cell surface as shown by indirect immunofluorescence and specific cytotoxicity with rabbit anti-idiotypic antiserum. Fluorescence and cytotoxicity are inhibited by 141 IgM but not by 104E IgM, a monoclonal IgM produced by a BALB/c plasmacytoma. Immunization of B/W mice with 141 IgM before transplantation of lymphoma 141 confers protective immunity. No such protection occurs after immunization with 104E IgM or other unrelated proteins. Protected mice contain spleen cells cytotoxic for 141 lymphoma cells. This cytotoxicity is blocked by incubation of spleen cells with 141 IgM but not with 104E IgM. Moreover, splenic lymphocytes from protected mice are stimulated to synthesize DNA by 141 IgM but not by 104E IgM. These results suggest that specific cellular immune responses to idiotypic determinants may participate in the observed protection against challenge with the corresponding B-cell tumor.

Animals↗

Thymosin corrects the abnormal DNA synthetic response of NZB mouse thymocytes.

New Zealand Black (NZB) mice develop after 16 weeks of age an autoimmune and lymphoproliferative disease which is a model for systemic lupus erythematosus and lymphoid malignancy in humans. At this age, the mice manifest a progressive decline in T lymphocyte (thymus-derived lymphocyte) functions and serum thymosin levels. Thymocytes from 8-week old NZB mice exhibit an abnormal DNA synthetic response when transplanted into lethally irradiated C57B1/6 recipients. DNA synthesis (measured as the incorporation of radioactively labeled 5-iodo-2'-deoxyuridine) is delayed in onset and still increasing 6 days after cell transfer. By contrast, 2-week old NZB thymocytes show a normal response which is rapid in onset and completed by day 6.NZB mice were injected with thymosin fraction 5 or with bovine serum albumin starting at 2 weeks of age. Thymocytes from 8-week old thymosin-treated mice showed a normal DNA synthetic response, whereas the albumin-treated controls showed the abnormal response expected at this age. The ability of thymosin to correct the DNA synthetic response was related to dose and duration of treatment. These results suggest that thymosin can induce a more normal state of thymocyte differentiation in NZB mice. If abnormal thymocyte differentiation is related to the subsequent emergence of autoimmunity and lymphoid malignancy, then continuous treatment with thymosin may have therapeutic potential. These experiments suggest that an endocrine disturbance may contribute to autoimmune and lymphoproliferative disease in NZB mice and possibly in humans.

Age Factors↗

T and B lymphocytes in peripheral blood and tissue lesions in Sjögren's syndrome.

Lymphocyte heterogeneity was studied in peripheral blood and salivary gland lesions in 24 patients with Sjögren's syndrome. Peripheral blood B cells, measured by immunofluorescence with specific antiserum to immunoglobulins or by rosette assay with complementcoated erythrocytes, were increased in most patients. Peripheral blood T cells, measured by immunofluorescence with rabbit antiserum to human thymocytes or by rosette assay with sheep erythrocytes, were reduced in eight patients. Three had associated rheumatoid arthritis, two had a generalized lymphoproliferative disorder, and one each had scleroderma, systemic lupus erythematosus, and neuropathy. The salivary gland lymphocytic infiltrates present in labial biopsy specimens were compared in 10 patients using an indirect immunofluorescent method with anti-human T cell serum and a quantitative focus-scoring method. In general, there was a correlation between the number of T cells and the extent of the infiltrate. Striking accumulations of T cells were present in some patients, but clusters of presumed B cells were also seen. These results indicate an increase in peripheral blood B cells in most patients, a decrease in T cells in some, and a mixed T and B cell infiltrate in the salivary gland lesions.

Adult↗

Monoclonal macroglobulinemia in NZB-NZW F1 mice.

Serum monoclonal macroglobulins were detected in over 30% of NZB/NZW F(1) mice greater than 11 mo of age. The monoclonal nature of the IgM was shown by restricted electrophoretic mobility, characteristic appearance on immunoelectrophoresis, restriction to a single light chain type, and ability to induce anti-idiotypic antisera. The monoclonal macroglobulins were separated from antibodies to DNA and RNA that migrated in the 7S region of sucrose gradients. Enlarged lymph nodes were often present in mice with monoclonal IgM, and a transplantable IgM-producing lymphoid tumor was established from the spleen of one animal.

Animals↗