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Lymphocytotoxic antibodies in SLE patients and their relatives.

A search for lymphocytotoxic antibodies in 50 SLE patients and in 109 of their blood relatives revealed an incidence of cold-reacting antibodies of 80% and 39% respectively, as compared with 15% in 110 normal blood donors paired for age, sex, and racial origin. The antibodies were also present in 7 of 18 (39%) of the spouses of SLE patients. Lymphocytotoxic antibodies exhibited broad reactivity in all groups, although positive SLE sera showed a tendency to react with a wider variety of lymphocytes and to present higher titers than positive sera from the other groups tested.

Animals

Nature of cold-reactive antibodies to lymphocyte surface determinants in systemic lupus erythematosus.

Antilymphocyte antibodies in serum from patients with systemic lupus erythematosus (SLE), as detected by microcytotoxicity and indirect immunofluorescence, were predominantly cold reactive and of the IgM class. These IgM antibodies were most active at 4 degrees C. IgG antibodies were infrequent, and were only minimally lymphocytotoxic. Most sera were cytotoxic for autologous lymphocytes and were equally reactive with normal and SLE lymphocytes, as well as with B- and T-cell preparations. Separate T- and B-cell specificities, which appeared not to be related to HL-A determinants, were identified by differential absorption experiments. The functional significance of these antilymphocyte antibodies is discussed.

Animals

Association of cold-reactive antilymphocyte antibodies with lymphopenia in systemic lupus erythematosus.

In a prospective study 26 of 29 patients with systemic lupus erythematosus had cold-reactive antilymphocyte antibodies cytotoxic for autologous lymphocytes and lymphocytes from normal subjects. The level of antilymphocyte antibodies was highly correlated, by linear regression analysis, with lymphopenia in these patients. The data suggested that both the avidity and the concentration of these antibodies were important determinants in this relationship. A clear association between increased antilymphocyte antibody activity and exacerbation of SLE was demonstrated. Apart from lymphopenia, however, neither type of clinical manifestation nor any particular serologic abnormality appeared to be related to the presence of antilymphocyte antibodies.

Antibodies

Lymphocytotoxic antibody activity in cryoprecipitates from serum of patients with SLE.

Complement-dependent cytotoxic activity against normal human peripheral blood lymphocytes was detected in 11 of 17 cryoprecipitates from the serum of patients with systemic lupus erythematosus (SLE). The lymphocytotoxicity was eliminated by treatment with 2-mercaptoethanol and iodoacetamide, and it was inhibited by antibody to human IgM but not anti-IgG. The titers of lymphocytotoxic activity in the cryoprecipitates were roughly proportional to the corresponding serum titers, but when they were normalized for IgM concentration it was apparent that selective concentration of lymphocytotoxic antibody occurred in the cryoglobulins. The relationship between cryoprecipitable lymphocytotoxicity and a number of laboratory and clinical parameters of SLE was studied. The amount of protein in the cryoprecipitates, which was greatest in patients with significant renal disease, correlated with a reduction of serum complement and the amount of antibody to DNA. However the lymphocytotoxic activity of the cryoglobulins did not correlate with the severity of SLE. The titer of lymphocytotoxic antibody was independent of a) the presence or absence of active lupus nephritis, b) the total protein or immunoglobulin content of the cryoprecipitates, c) serum complement levels, and d) the amount of circulating antibody to DNA. These findings cast doubt upon the pathogenetic significance of cryoprecipitable lymphocytotoxic antibody.

Antibodies

Production of migration inhibitory factor and lymphotoxin by non-T cells.

Treatment of tuberculin-sensitive guinea pig spleen or lymph node cells with a burro anti-T cell serum plus complement diminished markedly the number of functionally detectable T cells, but did not affect the amount of migration inhibitory factor (MIF) or lymphotoxin produced by the residual T cell-depleted populations.

Animals

The effect of a lymphotoxic factor from patients with multiple sclerosis on acute lymphosarcoma cell leukemia and acute lymphoblastic leukemia.

Eight patients with acute lymphosarcoma cell leukemia or acute lymphoblastic leukemia received infusions of plasma containing a lymphotoxic factor. The lymphotoxic factor induced a transient fall in the number of "blast" cell forms in the peripheral blood in six of the eight patients but did not produce sustained remissions. Previous investigations have demonstrated that this lymphotoxic factor, found in the plasma of patients with active multiple sclerosis, is of low molecular weight and does not have the properties normally associated with an antibody. This factor appears to selectively interfere with ribonucleic acid synthesis in the thymus-derived lymphocyte. Lymphotoxic factor activity was demonstrated in the serum of one patient during a remission in leukemia induced by a viral illness.

Adolescent

Activation of human T-lymphocytes. A kinetic and stereological study.

Stereological data of phytohaemagglutinin (PHA)-activated human T-lymphocytes were recorded at intervals (12 to 72 h) together with biochemical (isotope-uptake, lymphotoxin-release) and morphological measurements. About 98% of the cells were activated 12 h after PHA-stimulation. The activation phase lasted less than 48 h, i.e., cells entering the activation phase within 12 h were at their activation maximum by 48 h. The activated cell increased in size. The nuclear/cytoplasmic-ratio decreased. Most of the cytoplasmic organelles developed in phase with the increase of cytoplasmic volume. After 48 h, mitotic figures were frequently seen. Due to the increasing number of secondary, activated daughter cells, parameters of most cytoplasmic components declined between 48 and 72 h. Structural changes in the nucleus preceded the 3H-leucine uptake, which had not reached its maximum after 72 h of incubation. The 3H-leucine uptake started as early as 12 h after culture initiation, and its increase was proportional to the increasing polyribosome density. No maximum uptake was reached up to 72 h, but the development of structural components related to this uptake was at its maximum at the end of the activation phase (48 h). The formation of bound ribosomes occurred subsequent to the enlargement of the surface of the rough endoplasmic reticulum. Initial polysome formation occurred at the expense of existing free ribosomes.

Adult

Interstital nephritis in autoimmune hemolytic anemia.

A case is reported of a 15-year-old boy with chronic autoimmune hemolytic anemia who developed renal insufficiency 3 years after splenectomy. An interstitial nephritis with striking lymphocytic infiltrates and sclerosed glomeruli could be demonstrated by percutaneous renal biopsy. Renal symptoms disappeared promptly after corticosteroid therapy. The renal lesions are thought to have arisen as part of the autoimmune disease.

Adolescent

[Cold-lymphocytotoxic antibodies in the sera of cervix-carcinoma patients].

Sera of 120 patients with cervical cancer were screened for cold reacting, complement dependant autolympho-cytotoxins (CoCoCy). These antibodies occurred in 21,7% of the patients in comparison with 11,2% of 116 controls. The highest percentage of CoCoCy-antibodies was detected in the sera of patients with cervical cancer stage I (27,6%). Thus demonstration of CoCoCy-antibodies may be of pathogenetic rather than of diagnostic interest. CoCoCy-antibodies could be seen to reflect autoimmune reactions in cervical cancer.

Autoantibodies

[Suppression of the cell-mediated immunity in minor histoincompatible rat kidney allograft recipients (author's transl)].

To study the immunological status of recipients of major compatible and minor incompatible kidney allografts, we transplanted FiS and FLF1 kidneys into LEW rats. Most of the FiS kidneys were rejected within 55 days. Of 24 recipients, only 4 survived longer than 4 months. However, two-thirds of the FLF1 recipients survived longer than 4 months. The other third died with 64 days. During the first postoperation week a high level of lymphocytotoxin was detected in the serum of the FiS kidney recipients. Thereafter hardly any alternation of its titer was found, and no variation among the recipients of major histocompatible kidney allografts was shown. The FLF1 kidney recipients showed a low titer of antibody. The hemagglutinin titer showed the same trend as the lymphocytotoxin titer. A blocking serum factor could not be found in the serum of the kidney recipients with the microcytotoxity assay method or with the allorosette-formation inhibition test. Cellular immunity, which was studied with the GvH-reaction and microcytotoxity assay, was detected in the first postoperative week. However, this immunity was gradually supressed, and after 6 weeks was no longer to be found. This immunological status remained unchanged in the indefinitive surviving kidney-recipients in spite of antigen inoculation with two skin allografts of donor origin. This immunological status could be defined as "graft acceptance".

Animals