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Biomedical subjects

J M Zarling

Publications and source records attributed to J M Zarling.

At least 55 records · Page 3Linked to original sources
PubMed1980

Requirements for T cells in alloantigen-induced generation of non-T cell-mediated cytotoxicity against syngeneic mouse sarcoma cells.

In vitro stimulation of BALB/c spleen cells with allogeneic normal cells results in the generation of effector cells cytotoxic for syngeneic SV40 virus-induced MKSA fibrosarcoma cells. The conclusion that natural killer (NK) cells are activated that lyse the syngeneic tumor cells derives from findings that 1) treatment of the allostimulated BALB/c effector cells with anti-theta serum and complement does not ablate cytotoxicity against syngeneic MKSA tumor cells and 2) allostimulation of congenitally athymic (nu/nu) BALB/c mice results in significant cytotoxicity against MKSA tumor cells but not against allogeneic target cells. The requirement for the presence of theta-positive cells in alloantigen-induced activation of NK cells cytotoxic for syngeneic tumors was studied. Spleen cells from conventional BALB/c mice are cytotoxic for syngeneic MKSA tumor cells after stimulation with anti-theta serum-treated allogeneic cells or with allogeneic nude cells. In contrast, stimulation of BALB/c nude spleen cells with anti-theta serum-treated allogeneic cells or allogeneic nude cells fails to give rise to anti-tumor effector cells. Thus, theta-positive cells (presumably T cells) are required for alloantigen induced non-T cell-mediated lysis of syngeneic tumors.

Animals↗
PubMed1979

Elicitation of anti-leukemia cytotoxic responses.

We have presented the rationale for the in vitro approaches that we have taken for generating cytotoxic lymphocytes capable of lysing autologous leukemia cells or leukemia cells from HLA identical siblings. Two different approaches have been used, both of which are based on earlier findings concerning the antigenic and cellular interactions involved in the generation of strong cytotoxic responses to alloantigens in mixed leukocyte culture.

Cytotoxicity, Immunologic↗
PubMed1978

Sensitization of lymphocytes against pooled allogeneic cells. I. Generation of cytotoxicity against autologous human lymphoblastoid cell lines.

Lymphocytes sensitized in vitro to a pool of X-irradiated allogeneic normal lymphocytes from 20 individuals develop cytotoxic activity for autologous human lymphoblastoid cells (LCL). Whereas pool sensitized T lymphocytes lyse autologous LCL cells, they fail to lyse autologous B-enriched or T-enriched normal target cells nor autologous phytohemagglutinin (PHA) blasts. In contrast to pool sensitization, stimulation with normal cells of single allogeneic individuals rarely led to development of cytotoxicity against autologous LCL cells. We conclude that human Epstein-Barr virus transformed LCL cells express target antigens cross-reactive with allogeneic target antigens expressed on normal cells and that sensitization with a pool of allogeneic cells is an effective means of generating effector cells directed against autologous abnormal cells.

B-Lymphocytes↗
PubMed1978

Pool-priming: A means of generating T lymphocytes cytotoxin to tumour or virus-infected cells.

It is proposed that cells cytotoxic for autologous or syngeneic tumour cells can be produced in vitro by sensitisation of lymphocytes to a pool of normal cells from 20 unrelated individuals. Restriction on molecules that can serve as cytotoxic determinants (C.D.), may explain why a random pool of cells from 20 people could present essentially all of the determinants (C.D.) may explain why a random pool of occur because of extensive cross-reactivity of antigens on tumour cells with normal alloantigens present in the stimulating pool.

Antigens, Neoplasm↗
PubMed1978

Alloantigen-induced enhancement and suppression of human cytotoxic lymphocyte responses to autologous lymphoblastoid cell lines.

In vitro sensitization of human lymphocytes to autologous lymphoblastoid cell lines (LCL) has been shown to give rise to cytotoxic lymphocytes capable of lysing autologous as well as allogeneic LCL cells. However, allogeneic LCL cells were found to be markedly less effective than autologous LCL cells in terms of generating lymphocytes capable of lysing autologous LCL cells. The addition of allogeneic LCL cells or allogeneic normal lymphocytes to a mixture of responding lymphocytes and X-irradiated autologous LCL cells suppressed the generation of cytotoxic lymphocytes against autologous LCL cells. Furthermore, suppressor T cells generated in allogeneic mixed leucocyte culture (MLC) and supernatants from MLC likewise decreased the generation of cytotoxic lymphocytes to X-irradiated autologous LCL cells. In contrast to the findings that alloantigens suppress the generation of cytotoxicity of X-irradiated autologous LCL cells, which ordinarily induce strong cytotoxic responses, were the findings that allogeneic stimulating cells and supernatants from MLC enhanced cytotoxic responses to autologous ultraviolet light or extensively heat-treated LCL cells that induce weaker cytotoxic responses. The possible mechanisms whereby alloantigens enhance or suppress cytotoxic responses to autologous abnormal cells and the implications of these findings are discussed.

Cell Line↗
PubMed1978

Enhancement of T cell cytotoxic responses by purified human fibroblast interferon.

Purified polyribonucleotide-induced human fibroblast interferon (HFIF) was tested for its effects on proliferative and cytotoxic human T cell responses to alloantigens. The addition of HFIF (100 to 400 IFU/ml) to mixed leukocyte cultures decreased alloantigen-induced lymphocyte proliferative responses as determined by both recovery of responding cells and by 3H-thymidine incorporation into responding cells. However, HFIF, but not the mock interferon preparation, increased the cytotoxic response of T cells to allogeneic cells by 4- to 5-fold when expressed in terms of lytic units. Although fibroblast and leukocyte interferons have different physicochemical and biologic properties, the results reported here are in concert with previous findings concerning the effects of virus-induced leukocyte interferon on human T cell functions.

Cytotoxicity, Immunologic↗
PubMed1976

A sensitive micromethod for generating and assaying allogeneically induced cytotoxic human lymphocytes.

A sensitive micromethod for generating and assaying allogeneically induced cytotoxic human lymphocytes in vitro is described. Responding lymphocytes are cultured with mitomycin-C treated allogeneic stimulating cells in wells of replicate microtrays for both one-way mixed leukocyte culture (MLC) and cell-mediated lympholysis (CML) assays. On day 5, MLC response is determined by measuring 3H-thymidine (3H-TdR) incorporation directly in wells of the MLC tray. On day 6 or 7 CML response is determined by measuring 51Cr released from labeled target cells added to replicate culture cells in the CML tray. It is thus possible to measure both MLC and CML responses of the 2.5 X 10(4) -U X 10(5) responding lymphocytes originally placed in replicate wells. 51Cr-labeled target cells can be added to wells containing dilutions of the stimulated cells and a log-linear relationship between the per cent specific 51Cr release and number of effector cells is observed. Significant levels of specific cytoxicity are detected at ratios as low as one effector cell per target cell; little cross-killing on third-party cells and no autokilling is observed. Lymphocytes purified from whole blood that is stored overnight at room temperature and purified lymphocytes stored overnight in the cold generate MLC and CML responses comparable to those of lymphocytes purified from fresh blood. Only 2 or 3 ml of whole blood are required to perform both MLC and CML assays, thus enabling the study of both proliferative and cytotoxic lymphocyte responses in young children and other individuals from whom only a few milliliters of blood can be obtained.

Blood Preservation↗
PubMed1975

Lysis of leukemia cells by spleen cells of normal mice.

Spleen cells from 2- to 3-month-old normal mice of some strains having a low incidence of spontaneous leukemia were found to lyse cells of the spontaneous AKR leukemia K36 in the 51Cr release assay. Incubation of 51Cr-labeled ADR K36 cells with spleen cells from normal C57BL/6, C57L, C57BL/10, and RF mice resulted in the release of significantly more 51Cr than that released in the presence of medium alone. In contrast, 51Cr released from AKR K36 cells after incubation with spleen cells from mice of the high leukemic strains AKR and C58 was less than that released spontaneously. The results of competitive inhibition tests when C57BL/6 spleen cells were incubated simultaneously with 51Cr-labeled AKR K36 target cells and varying numbers of nonlabeled cells demonstrated that the cytotoxic activity of normal C57BL/6 spleen cells was directed against an antigen(s) associated with several leukemias, but that was undetectable on normal thymocytes. Pretreatment of C57BL/6 spleen cells with carbonyl iron and a magnet, which removed phagocytic macrophages, did not decrease the cytotoxic acitivity for AKR K36 cells.

Animals↗