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Biomedical subjects

H Warnatz

Publications and source records attributed to H Warnatz.

At least 19 recordsLinked to original sources

Kinetics of cytokine secretion by mononuclear cells of the blood from rheumatoid arthritis patients are different from those of healthy controls.

Mononuclear cells from peripheral blood (PBMC) of rheumatoid arthritis (RA) patients and healthy controls were incubated with alpha-CD3. Cytokine secretion from 2 h to 72 h of incubation was measured by ELISA. There were no significant differences in secretion of T cell derived IL-2 and IL-4 in cultures from RA patients and controls. The macrophage-derived cytokines, IL-1 beta and tumour-necrosis factor-alpha (TNF-alpha) were secreted with a steep increase of concentration during the first 16 h of incubation by PBMC from RA patients. PBMC from healthy controls secreted both cytokines at a constantly rising rate with a maximum for TNF-alpha at 48 h and for IL-1 beta at 72 h. Interferon-gamma (IFN-gamma) is secreted in significantly reduced concentrations by PBMC from untreated RA patients compared with controls. Gold-salt treatment led to a slightly delayed and enhanced secretion of TNF-alpha and IL-1 beta, an enhanced secretion of IL-2 and a restored secretion of IFN-gamma.

Antigens, Differentiation, T-Lymphocyte

Antibody-dependent cell-mediated cytotoxicity (ADCC) and cell-mediated cytotoxicity (CMC) to HBsAg-coated target cells in patients with hepatitis B and chronic hepatitis (CAH).

A new technique using HBsAg-coated Chang cells as target cells was developed in order to measure cell-mediated immune reactions to HBsAg. The specificity of cytotoxic reactions was tested in experiments using Chang cells conjugated with human serum albumin. Antibody-dependent cell-mediated cytotoxicity (ADCC) specific for the HBsAg-coated target cells was demonstrated up to dilutions of anti-HBsAg serum of 10,000 : 1, when lymphocytes from the peripheral blood of normal individuals were added to the target cells. Spontaneous cell-mediated cytotoxicity (CMC) to HBsAg-coated target cells was demonstrated for lymphocytes from patients with hepatitis B and from patients with chronic active hepatitis (CAH), but not for lymphocytes from healthy controls. The CMC of hepatitis B lymphocytes to HBsAg-coated target cells was inhibited in the presence of antiserum to HBsAg. In experiments using purified lymphocyte populations evidence is presented that the CMC is T-cell dependent. HLA-restriction of the CMC was not observed. The described cytotoxicity test system has the advantage that target cells conjugated with defined antigens are used and that relevant control target cells are available.

Antibody-Dependent Cell Cytotoxicity

Kartagener's syndrome in sibs: clinical and immunologic investigations.

In a sibship of ten children descending from a first cousin's marriage, two sibs were affected by Kartagener's syndrome with the typical symptoms of situs inversus, bronchiectasis, and polyposis nasi. Clinical investigation of the entire family revealed chronic infections of the paranasal sinus in five sibs and the mother, two of whom had bronchiectasis as well. Immunologically, a persistent cellular or humoral defect could not be detected in any of the family members. In the HLA system, only the two sibs with Kartagener's syndrome had identical HLA-types; all other family members had different combinations. A linkage between the loci for the HLA system and Kartagener's syndrome is discussed.

Adolescent

Studies on lymphocytotoxicity in acute and chronic liver disease.

The cytotoxicity of lymphocytes from patients with chronic active hepatitis, chronic persistent hepatitis, acute hepatitis B and rheumatoid arthritis as well as from normal controls was studied in a microcytotoxicity assay according to COHEN et al. using 125I-iododeoxyuridine labeled embryonal liver cells and Chang cells as target cells. Unfractionated lymphocytes of the peripheral blood from patients with chronic active hepatitis and rheumatoid arthritis showed a high frequency of cytotoxic activity. The lymphocytotoxicity in chronic active hepatitis was significantly increased in comparison to normal controls at the EC/TC of 10:1 and 100:1. Specificity of the cytotoxic reaction to target cells could not be demonstrated. Addition of autologous serum to the cytotoxic assay blocked the lymphocytotoxicity in patients with chronic active hepatitis. A weak potentiating effect on lymphocytotoxicity was observed in patients with hepatitis B after addition of autologous serum. It is discussed that this reaction is due to the presence of HB-antigen in the serum since addition of HB-antigen from other sources increased also the lymphocytotoxicity in hepatitis B patients. This effect was observed neither in HB-antigen positive nor in HB-antigen negative patients with chronic active hepatitis or chronic persistent hepatisis.

Acute Disease

The significance of cytotoxicity of lymphocyte populations in coloncarcinoma patients in comparison to normal controls using a new statistical method of evaluation.

Lymphocytotoxicity was studied in patients suffering from colon carcinoma. 125Iododeoxyuridin-labeled established colon carcinoma cells were used as target cells in a cytotoxicity assay according to COHEN et al. (1). They were incubated with unfractionated lymphocytes of the peripheral blood, purified T cells or adherent cells as effector cells. The cytotoxic effect was measured in cpm, i. e. the radioactivity released from the target cells into the supernatant. The cpm were adjusted by eliminating the variables of spontaneous release and for maximal incorporated radioactivity of the target cells. The cytotoxic activity of lymphocytes to colon carcinoma target cells was dose-dependent. It was demonstrated for lymphocytes from colon carcinoma patients as well as for lymphocytes from healthy controls. Although adjusted cpm values were used for statistical analysis lymphocytes from the 20 colon carcinoma patients did not show a higher cytotoxic effect than lymphocytes from the 20 healthy controls. However, when the results were compared separately for each experiment consisting of 2 colon carcinoma patients and 3 healthy controls, statistical significant specific lymphocytotoxicity was demonstrated for lymphocytes from colon carcinoma patients. The plot diagram of the results and the statistical evaluation by the multivariate analysis of variance (Manova) offer a clear and comprehensible representation of the results. Particularly for statistical reasons, this representation is superior to the usual calculation of percent specific lysis. It was demonstrated in this study that the cytotoxic activity in the absence of autologous serum is a function of T cells of the peripheral blood. Adherent cells have a high cytotoxic activity regardless whether the cells were obtained from colon carcinoma patients or from healthy controls.

Adenocarcinoma

Lymphocytotoxicity to tumor target cells and interference of serum factors or tumor antigen with lymphocytotoxicity in patients suffering from different stages of breast carcinoma.

The in vitro cytotoxicity of lymphocytes from patients suffering from breast carcinoma against autochthonous, allogeneic and established breast carcinoma cells was evaluated. Lymphocytotoxicity to breast carcinoma cells was observed in all stages of the disease. Control lymphocytes from healthy donors or patients suffering from other carcinoma are not cytotoxic for the breast carcinoma cell lines. A follow-up study of the cell mediated immune reactions before and after surgical removal of the breast carcinoma showed that the cytotoxic lymphocyte population which is demonstrated in the presence of the tumor disappears quickly after excision of the carcinoma. The non-reactivity of lymphocytes is not due to a general immune defect. Serum of the tumor bearers did not block the lymphocytotoxicity in early stage breast carcinoma; in metastatic disease inhibition occurred in more than half of the cases. Preincubation of lymphocytes with antigen preparations of allogeneic breast carcinoma cells did not inhibit the cytotoxicity to breast carcinoma cells whereas autologous serum preincubated with the antigen preparation diminished the lymphocyte reactivity to the target cells in some cases.

Adult

Studies on the specificity of in vitro induced lymphocytotoxicity to SV40-transformed fibroblasts.

Cytotoxic effector lymphocytes were induced by in vitro immunization of lymph node and spleen cells from AKR-mice (H-2k) and from BALB/c-mice (H-2d) to syngeneic SV40-transformed fibroblasts. The T cell-dependent cytotoxicity was specific for target cells expressing the same H2-specificity as the immunizing cells. Nontransformed fibroblasts as stimulator cells did not induce efficient cytotoxicity to transformed or nontransformed target cells. Incubation with phytohemagglutinin during the sensitization period modified the specificity of the T cell-mediated lysis of syngeneic SV40-transformed fibroblasts: allogeneic as well as syngeneic target cells were destroyed by these effector cells. However, the polyclonal stimulant activates preferentially cytotoxicity to H2-matched target cells. The in vitro generation of cytotoxic effector cells was restricted to living SV40-transformed fibroblasts as immunizing cells; it was not possible to immunize lymphocytes in the presence of membrane proteins prepared from the SV40-transformed cells. The cytotoxicity of the in vitro immunized lymphocytes was inhibited by incubation with membrane protein preparations from syngeneic or allogeneic SV40-transformed fibroblasts.

Animals

[Long term treatment of rheumatoid arthritis. Experiences with D-penicillamine in comparison with gold and immunosuppressive drugs (author's transl)].

In a controlled trial including 80 patients suffering from different stages of rheumatoid arthritis it was demonstrated that D-penicillamine therapy favourably influences the clinical course of the disease as compared to a control group treated with antirheumatic drugs. Particularly the therapy continued over one year resulted in a significant fall of the joint and activity index as well as of the BSR. Side effects were observed in more than half of the cases. Renal, hematological and severe exanthematic complications forced to discontinue the administration of D-penicillamine in 6 of 41 cases. As compared to other therapeutics our study indicates that D-penicillamine and gold treatment are equivalent drugs in rheumatoid arthritis whereas immunosuppressive drugs are reserved for severe cases of rheumatoid arthritis because of their strong side effects.

Adolescent

Studies on the cytotoxic effect of in vivo and in vitro immunized lymphocytes on liver target cells.

Lymph node and spleen cells from mice immunized in vivo to allogeneic of syngeneic liver antigen are cytotoxic for syngeneic liver cells, but not for syngeneic fibroblasts or established liver cell cultures of allogeneic origin. The cytotoxic activity is mainly dependent on T-cell activity, but a non-T-cell-mediated cytotoxicity may also play a role. Lymphocytotoxicity is inhibited by preincubation of the lymphocytes with syngeneic liver antigen, but not with syngeneic kidney homogenate. The liver-specific lymphocytotoxicity corresponds to the in vivo function of lymphocytes in the development of experimental hepatitis. In vitro immunization of lymphocytes in a Mishell-Dutton culture system also induces liver-specific cytotoxicity. The results indicate that the natural tolerance to self antigens can be lost after invivo as well as in vitro immunization. The induction of self-reactivity of lymphocytes in these experiments may be attributed to regulatory mechanisms of the immune reaction at a cellular level.

Animals