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Biomedical subjects

J L McCoy

Publications and source records attributed to J L McCoy.

At least 73 records · Page 4Linked to original sources
PubMed1976

Cell-mediated immunity in mice against papain-solubilized histocompatibility and tumor-specific antigens by a macrophage migration inhibition microassay.

The cell-mediated immune status of B10.D2 (H-2d) mice immunized with spleen cells from a congenic strain, B10.A (H-2a), differing at the H-2 locus and of BALB/c mice immunized with a syngeneic simian virus 40 (SV40)-induced sarcoma (mKSA-TU5) was evaluated by an agarose microassay for migration inhibition factor. The inducing antigens in this experiment were papain-solubilized and partially purified chromatographic preparations of spleen cells from A/J mice (H-2a) and a papain-solubilized antigen extract prepared from a tissue culture-adapted cell line (TU-5), derived from the SV40-induced mKSA tumor. The assay used microliters of normal or immune peritoneal exudate cells (PEC) resuspended in a 2-mul droplet of agarose and cultured in the presence or absence of antigen. Specific migration inhibition of PEC from immunized mice was observed with concentrations of solubilized antigen preparations as low as 2.0 mug/ml (3.67 mug/chamber).

Animals↗
PubMed1976

Leukocyte migration inhibition by soluble extracts of MCF-7 tissue culture cell line derived from breast carcinoma.

Studies were conducted to determine whether MCF-7, a tissue culture cell line derived from a pleural effusion of a patient with breast carcinoma, could be used as a source of tumor-associated antigen for direct leukocyte migration-inhibition (LMI) assays. Of 32 patients with breast carcinoma, 27 (84.4%) gave positive migration-inhibition results on their initial tests with a 25-mug protein/ml concentration of a 3 M KCl extract of MCF-7; 1 of 24 (4.5%) normal donors reacted with MCF-7. An intermediate incidence of reactivity (7/16) was observed with the extract when leukocytes of patients with melanoma, lung carcinoma, and Ewing's sarcoma were used. In further specificity studies, leukocytes of patients with breast carcinoma gave a lower incidence of LMl reactivity than did those of patients with Ewing's sarcoma and lung carcinoma with KCl extracts of the appropriate histologic type of tumor. The results indicated that the MCF-7 cells possessed a tumor-associated antigen to which many patients with breast carcinoma are sensitized.

Antigens, Neoplasm↗
PubMed1975

Cellular immune reactivity in vitro and tumor rejection provided by tumor-associated antigens of friend-virus-induced leukemia.

Cell-mediated immunity (CMI) and tumor rejection were studied in the Friend virus leukemia system of C57Bl/6 mice. Mice were immunized with Friend leukemia virus (FLV) or X-irradiated FBL-3 leukemic cells and studied temporally for the development of CMI reactivity by assays of 51Cr release lymphocyte cytotoxicity, lymphocyte transformation, migration inhibition, Winn tumor cell neutralization and transplantation rejection. High levels of specific lymphocyte cytotoxicity were observed by day 7 f0llowing FLV infection; this reactivity reached a peak between 17 and 21 days, and returned to background levels by day 36. Further, positive Winn assays were obtained with spleen cells from mice immunized with FLV at times when the mice resisted live FBL-3 tumor challenge. Positive lymphocyte transformation was obtained with spleen cells from mice immunized with FLV or FBL-3, but not with cells from normal mice or mice immune to a syngeneic methycholanthrene-induced tumor, when cultured with papain-soluble FBL-3 or RBL-5 tumor-cell extracts or mitomycin-C (MMC)-treated FBL-3 or RBL-5 cells. Positive reactivity in the lymphocyte transformation assay occurred after reactivity had peaked in the lymphocyte cytotoxicity test. Similar positive macrophage migration inhibition patterns were also obtained with peritoneal exudate cells (PEC) from FLV-immunized mice using papain-solubilized tumor-associated antigen (TAA) from FBL-3 cells. These data suggest that sequential development and modulation of CMI reactivity occurs as observed in different assays following immunization in this system.

Animals↗
PubMed1975

Studies of lymphocyte stimulation by intact tumor-cell and solubilized tumor antigen.

BALB/c mice were rendered immune to syngeneic SV40-induced sarcoma by subcutaneous injection of mKSA-TU5 tissue-culture adapted cells. Spleen cells from immune mice were examined for tumor-cell neutralization in the Winn assay as well as in in vitro lymphocyte stimulation assays. A microculture (200 mul) lymphocyte stimulation (LS) assay utilizing immune spleen cells was employed with mixed lymphocyte/tumor-cell cultures (MLTC) and the papain crude soluble (CS) extracts from mKSA-TU5 cells. Specificity in the LS assay was determined using spleen cells from mice immune to other syngeneic tumors and by soluble antigenic preparation of normal BALB/c spleen cells. The Winn assay studies demonstrated that spleen cells from mKSA-sensitized mice neutralized mKSA tumor cells and this was corroborated by their resistance to direct tumor challenge. Positive lymphocyte transformation responses in MLTC were observed when mKSA-TU5-sensitized spleen cells were mixed with mitocycin-C-treated intact tumor cells or when papain-solubilized antigens of mKSA cells were employed, but not with non-immune spleen cells or with a soluble antigen from normal cells. Papain-solubilized antigen preparations employed in in vitro assays also immunized against challenge with mKSA tumor cells. Specificity of these lymphocyte transformation reactions was demonstrated with non-sensitized lymphoid cells or lymphoid cells from mice sensitized with a syngeneic Kirsten virus-induced respond. Thus, mKSA tumor surface antigens were recognized on intact tumor cells or with microgram quantities of papain-solubilized extracts from these tumor cells. We believe the lymphocyte stimulation assay affords a method for demonstrating the presence of tumor-specific antigen and for monitoring further purification procedures.

Animals↗
PubMed1975

Cell-mediated immunity to melanoma-associated antigens in patients with ocular malignant melanoma.

We tested 11 patients with choroidal melanomas and 32 control subjects for cell-mediated immunity to melanoma-associated antigens by an in vitro leukocyte migration inhibition assay. Five of seven patients with choroidal melanomas, who received two melanoma extracts used in this series of experiments, had significant leukocyte migration inhibition as compared with none of 17 normal subjects. Four of five melanoma patients who received a third melanoma extract had significant leukocyte migration inhibition as did three of four normal controls, indicating that the extract showed nonspecific inhibition. These data agreed with the concept that patients with choroidal melanomas have cell-mediated immunity to common melanoma-associated antigens.

Antigens, Neoplasm↗
PubMed1975

Inhibition of leukocyte migration by tumor-associated antigens in soluble extracts of human malignant melanoma.

Direct leukocyte migration inhibition (LMI) assays were performed to investigate whether cell-mediated immune reactions could be detected in response to tumor-associated antigens of human melanoma. The antigens were 3 M KCl-soluble extracts of different fresh melanomas, other cancers, and benign nevus tissue. A total of 48 of the 79 (61%) blood samples from melanoma patients (64 patients) reacted with extracts of melanoma tissue. Since the subjects were usually tested with two or three extracts, 57/134 (42%) tests with melanoma patients' leukocytes were inhibited by KCl extracts of melanoma tissue, whereas only 3/50 (6%) tests with leukocytes of normal donors and 4/27 (15%) with patients having other cancers gave positive results. No positive reactions were obtained when 13 melanoma patients were tested with a 3 M KCl extract of benign nevus tissue. Likewise, only 2/26 (8%) positive tests were obtained from melanoma patients tested with extracts of other cancers. Individuals in all stages of disease had similar incidences of positive reactions to the soluble melanoma extracts, except for patients with stage-1 disease who exhibited a somewhat higher incidence of reactivity. The highest incidence of reactivity was observed in patients before surgical resection of the tumor, and somewhat decreased reactivity was seen 0-14 days post surgery. The results indicate that the direct LMI assay may be used to measure cell immune reactivity against melanoma-associated antigens. Since many of the positive results were obtained with allogeneic extracts, the results also indicate that different melanomas possess common antigens.

Adult↗
PubMed1975

Cell-mediated immunity in human acute leukemia.

The general cell-mediated immunological reactivity of patients with acute leukemia has been found to be intact, although it may be depressed by extensive disease or by chemotherapy. Patients with acute leukemia also have cellular immune reactivity against tumor associated antigens, as measured by skin tests for delayed hypersensitivity, lymphocyte stimulation, and 51Cr release cytotoxicity. Skin reactions to autologous and allogeneic crude membrane extracts of blast cells correlated with disease state, positive in many patients in remission and negative in most patients in relapse. Extracts of human lymphoid tissue culture cell lines derived from lymphomas or leukemia also gave positive reactions in patients with acute leukemia, and also in patients with lymphoma and nasopharyngeal carcinoma. The antigens detected in the skin tests with the lymphoid cell lines appear to be different from those associated with Epstein-Barr virus (EBV) and from those detected in the 51Cr release assay. Evidence is presented which suggests a complex variety of antigens on blast cells and on the cell lines. Although leukemia associated antigens were also detected by lymphocyte stimulation and by cytotoxicity assays, the results did not correlate with the skin tests nor with each other. The possible use of these assays for monitoring the chemotherapy and immunotherapy of acute leukemia patients is discussed.

Acute Disease↗
PubMed1975

In vitro human reactivity to staphylococcal phage lysate.

The cell-mediated reactivity of normal individuals to staphylococcal phage lysate (SPL) were tested in vitro in the lymphocyte stimulation (LS) and leukocyte migration inhibition (LMI) assays. There were 95% positive responses in LS (stimulation ratio larger than or equal to 3 with p less than 0.01) and 67% positive responses in LMI (migration index less than or equal to 0.80). Enriched subpopulations of T and B lymphocytes were prepared with rosette formation and density gradient centrifugation. SPL stimulated lymphoproliferative responses in both T and B cell subpopulations whereas phytohemagglutinin (PHA) stimulated only the T cell subpopulation. Cord blood leukocytes were tested in the LS assay and 41% gave positive responses to SPL, 81% to PHA, and 17% with SLO. SPL appears to be a useful reagent for the in vitro study of cell-mediated reactivity, and may provide somewhat different information from that obtained with other mitogens or antigens.

Antigens, Bacterial↗
PubMed1975

Humoral and cellular immunity to EBV and lymphoid cell line antigens in human lymphoma.

Although elevated antibody levels to the Epstein-Barr virus (EBV) have been reported in a number of lympho-proliferative neoplasms, it has not been possible to determine whether these antibodies were the result of a specific response to an oncogenic agent (EBV), whether they were a non-specific humoral compensation for depressed cell-mediated immunity (CMI), or whether a different mechanism was responsible. We have previously shown in a group of lymphoma patients that depressed cellular immunity to a number of standard antigens (Candida, SKSD, etc.) is not associated with an increase in antibody to EBV. In this study, we tried to compare CMI to possible EBV and lymphoid cell line antigens with humoral antibody to EBV. The two basis CMI assays utilized were lymphocyte cytotoxicity (LC) and skin testing (ST) for delayed hypersensitivity. In the LC assay, an EBV-containing cell line (F265) was used as the target. Reactivity against F265 was stronger in normal individuals than in cancer patients, suggesting a relationship to general cellular immune competence. ST studies showed that membrane extracts from lymphoid cell lines derived from patients with Burkitt's lymphoma and nasopharyngeal carcinoma (NPC) were more likely to elicit a delayed hypersensitivity in lymphoma and NPC patients than cell lines derived from normal individuals. Patients with ST reactivity against the membrane preparations from the tumour-derived cell lines were as likely to have elevated EBV antibodies as patients without such reactivity. The data strongly indicated that the elevated EBV titres in lymphoma patients are not related to a specific or non-specific depression of CMI.

Antibodies, Viral↗