Interferon determinations in evaluating the immune response.

IFNs are natural regulatory proteins with a variety of activities. The presence of IFN in the sera and the ability of lymphoid cells to produce IFN in vitro can be useful in the analysis of certain immunologically-mediated disorders. Moreover, analysis of the IFN system may be a very sensitive way to monitor chemically induced changes in immunity.

Role of the clinical immunology (veterinary) laboratory in determination of immunoglobulin abnormalities.

The focus of this discussion was to review selected immunologic techniques that can be helpful in characterizing immunoglobulin abnormalities. These methods are excellent tools to examine either subtle or drastic alterations in immunoglobulin production that may have arisen from modulation of the immune system with chemicals or selected drugs. It is important to stress that the immune abnormalities described and the methods used to evaluate these disorders do not separate the human and animal patient. In fact, some of the immunodeficiencies and autoimmune disorders outlined occur with striking similarity in both hosts. Therefore, expanding and improving the benefits of clinical immunology can provide better diagnosis and management of immunologic mediated disorders in both species.

Retinitis pigmentosa associated with a defect in the production of interferon-gamma.

Peripheral lymphocytes from patients with retinitis pigmentosa have a deficiency in their ability to produce the lymphokine, interferon-gamma. In 12 patients we found that peripheral leukocytes produced subnormal levels of interferon-gamma. These findings suggested that altered immune reactivity is one of the abnormalities associated with retinitis pigmentosa.

T-cell lymphoma occurring in the oropharynx.

Two cases of documented T-cell lymphoma occurring in the oropharynx are described. Both patients presented with cervical lymphadenopathy and involvement of oropharyngeal tissues. Although classification of these patients' lesions in relation to other known T-cell lymphomas was difficult, the location of the lesions in both cases and certain morphologic features in one case at least suggested that the malignant cells may have arisen from peripheral T-lymphocytes. In both patients, the neoplastic cells showed a tendency to impinge upon the oral epithelium, in keeping with the pattern of involvement of epithelial tissues seen in several varieties of T-cell lymphoproliferative disorders. The possibility that these oropharyngeal T-cell lymphomas may represent a distinct type of T-cell neoplasm is raised.

Prolymphocytic leukemia: treatment with combination chemotherapy to include doxorubicin.

Prolymphocytic leukemia (PL) is a clinically distinct leukemic disorder. Cytochemical and surface marker characteristics help to differentiate PL from other types of leukemia, including chronic lymphocytic leukemia (CLL). In contrast to patients with CLL, those with PL frequently require early therapeutic intervention. Standard treatment regimens for CLL as well as splenectomy and splenic irradiation have not been effective in the treatment of PL. Combination chemotherapy with cyclophosphamide, Doxorubicin, vincristine, and prednisone (CHOP) has produced impressive clinical responses in patients with PL. The treatment of a patient with PL is discussed and the literature is reviewed.

Gamma (immune) interferon production by leukocytes from a patient with a TG cell proliferative disease.

We report a patient with a disease characterized by proliferation of T cells with Fc receptors for IgG (TG). However, unlike lymphoid cells from normal individuals or from patients with other lymphoid malignancies, the patient's lymphocytes spontaneously produced gamma interferon (IFN-gamma) in vitro. The peripheral lymphocytes consisted of 95% TG cells, which exhibited the morphological characteristics of T-cell chronic lymphocytic leukemia (CLL) and were normal on cytochemical and chromosome analysis. The majority of TG cells were OKT3+, OKT8+, and OKT4-, 3A1-. These cells failed to express suppressor cell activity and displayed depressed levels of natural killer activity, but mediated antibody-dependent cell-mediated cytotoxicity. The spontaneous production of IFN-gamma by human peripheral lymphoid cells as demonstrated in this study may serve as a probe for studying the relationship between IFN-gamma and the proliferation of human T-cell subsets.

Naturally soluble tumor antigens from guinea pig hepatomas: isolation and partial characterization.

Naturally soluble tumor antigens were detected in the ascites fluid of guinea pigs bearing an ascites tumor and from exhausted tissue culture media of cultured tumor cells. Two antigenically distinct cell lines of diethylnitrosamine-induced strain-2 guinea pig hepatomas (line-10 and line-1) served as the source of tumor antigens. Tumor antigen activity was detected by four different techniques: immunodiffusion, inhibition of complement-mediated cytotoxicity, inhibition of membrane immunofluorescence, and delayed cutaneous hypersensitivity. With syngeneic tumor-specific antiserum, line-10 guinea pig tumor antigens were detected by immunofluorescence in the concentrated ascites and tissue culture fluids. With a xenogenic antiserum, demonstrated to be tumor specific, line-10 tumor antigens were detected not only in the concentrated ascites and tissue culture fluids but also in two of the partially purified fractions of these fluids. When the line-10 concentrated ascites and its fraction I were subjected to ultracentrifugation at 300,000 x G for 1 hr, the antigen activity was retained in the supernatant and thus by this criterion the tumor antigens detected in these samples are soluble. Immunodiffusion data indicate that more than one antigen is present in the line-10 system since three lines of precipitation were detected when line-10 concentrated ascites was reacted with the line-10 tumor-specific antiserum. In contrast to this, the line-10-concentrated tissue culture fluid displayed only one line of precipitation. Although tumor antigens could not be demonstrated in the other antigenically distinct tumor cell line, line-1, by immunodiffusion or inhibition of membrane immunofluorescence, inhibition of complement-mediated cytotoxicity was able to detect tumor antigens in the line-1 concentrated ascites and tissue culture fluids.

Quantitative comparison of techniques used to measure complement-mediated cytotoxicity of nucleated cells.

?The cytotoxicity of nucleated cells by specific antibody and complement can be guantitated in vitro by several methods. Trypan blue exclusion, 51-Cr release, inhibition of uptake of 3-H-thymidine, and inhibition of colony formation are the four assays that we used to guantitatively compare the C-mediated cytotoxicity of Chinese hamster lung (CHL) cells. CHL cells were sensitized with either guinea pig or rabbit anti-CHL antisera, and exposed to guinea pig, human, or rabbit C. We found that the relative activities of the antibodies and the complements were not dependent on the method of measurement of cytotoxicity, i.e., a given pair of antiserum-complement were not dependent on the method of measurement of cytotoxicity, i.e., a given antiserum-complement titer, regardless of the assay used to measure cytotoxicity. However, the titers of the different antibody-complement pairs differed from each other.