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J S Haskill

Publications and source records attributed to J S Haskill.

At least 55 records · Page 3Linked to original sources
PubMed1978

In situ Fc receptor-bearing cells in two murine tumors. I. Isolation and identification.

The in situ inflammatory response was studied in 2 different tumors, the T1699 mammary adenocarcinoma in inbred DBA/2 mice and a sarcoma induced in inbred C57BL/6 mice by murine sarcoma virus. The presence of Fc receptors (FcR's) on infiltrating host cells was determined by rosette formation with antibody-coated sheep red blood cells (EA). Differences in FcR-binding activity among various cells were detected with the use of EA prepared with a range of antibody concentrations. Cells bearing FcR represented one-third or more of the inflammatory cell population in both tumors. The FcR-positive cells were heterogeneous in regard to both cell type and FcR activity. Monocytes and macrophages had greater FcR activity than did lymphocytes. Different populations of FcR-positive cells could be isolated by their EA-binding characteristics.

Animals↗
PubMed1978

In situ cytotoxic T cells in a methylcholanthrene-induced tumor.

The in situ localization of cytotoxic T-cells was examined in a methylcholanthrene-induced fibrosarcoma. The MCA 2 tumor was initiated in this laboratory and utilized before extensive in vivo passage. Tumor cell suspensions were separated by unit velocity sedimentation. The T cell-enriched tumor-derived fractions and spleen cells from MCA 2-bearing mice were cytotoxic for in vivo isolated MCA 2 and in vitro cultured MCA 2 tumor cells, but not for SAD2 tumor cells. The cytotoxic activity of effector cells isolated from MCA 2 tumors was abrogated by treatment with anti-theta serum plus complement. The significance of cytotoxic T cells with in a progressing tumor is discussed.

Animals↗
PubMed1977

ADCC effector cells in a murine adenocarcinoma. I. Evidence for blood-borne bone-marrow-derived monocytes.

The origin and identity of effector cells for anti-body-dependent cell-mediated cytotoxicity and/or growth inhibition (ADCC) found in the murine mammary adenocarcinoma T1699 were investigated. Non-phagocytic, non-adherent ADCC effector cells were identified in bone marrow, peripheral blood and the host fraction of the tumor but not from lymphoid organs. These cells were shown to be distinct from the specific growth-inhibitory "armed monocytes" also identified in situ. The ADCC effector cells possess low levels of EA Fc receptors and appear to express a macrophage-associated antigen. Both the bone-marrow and the in situ effector cells became phagocytic after overnight incubation, providing further evidence for the monocyte-macrophage lineage of these cells. The results suggest that bone-marrow-derived blood-borne monocytes are the principal ADCC effector cells localizing in the mammary adenocarcinoma T1699. The parallels between tumor-induced immunity and cellular resistance to infectious agents involving hypersensitivity reactions and blood-borne monocytes are discussed.

Adenocarcinoma↗
PubMed1977

Immunologic responses to a murine mammary adenocarcinoma. I. Passive transfer of immunity by sera from tumor-bearing mice.

DBA/2 mice bearing a syngeneic mammary adenocarcioma T1699 produced high levels of tumor-specific antibody, detected by indirect immunofluorescence and subsequently identified as the IgG2a subclass. Tumor-bearer sera passively administered to normal recipients protected the animals from subsequent challenge with T1699 tumor cells butnot from challenge with a non-cross-reacting syngeneic tumor, SaD2 fibrosarcoma. Administration of sera prior to tumor challenge was found to be more effective than treatment after the challenge. The protective effect of sera appeared to parallel both antibody titers and appearance of concomitant immunity; however, sera absorbed with T1699 cells, with the indirect fluorescent antibody titers reduced more than 100-fold, conferred an almost identical level of protection. Immune suppression of serum recipients before serum transfer abolished the effect, suggesting that protection depended on a cellular immune response by the host in addition to the possible protective effect(s) of humoral antibody.

Adenocarcinoma↗
PubMed1977

The antibody response to the T1699 murine adenocarcinoma: antibody class and subclass heterogeneity detected in serum and in situ.

We have used indirect immunofluorescence to study antibody responses directed against membrane antigens expressed on in vitro and in vivo T1699 mammary adenocarcinoma cells. IgG1, IgG2a, IgG2b, IgG3, IgA, and IgM antibodies were present in the serum of DBA/2 mice bearing T1699 tumors; IgG2a and IgG2b antibodies were readily detected on the cells in situ. Lesser amounts of the other classes and subclasses could be detected by indirect immunofluorescence measurements on in vivo tumor cells and with low pH eluates of in vivo cells tested on the in vitro line of T1699. The antigenic determinants on in situ tumor cells are not saturated with antibody as these cells demonstrated enhanced fluorescence of all immunoglobulin classes and subclasses when treated with autologous serum. Experiments with thymus-depleted mice indicated that immunoglobulin production was strongly dependent on thymus-derived cells for all immunoglobulin classes and subclasses except IgG2b. Our studies suggest that IgG2a may be active in the macrophage-mediated cytotoxic reaction and IgG2b in the immediate hypersensitivity reaction to T1699 cells. These results provide further evidence for an active role of tumor-specific antibody in the host defense to the T1699 adenocarcinoma in situ.

Adenocarcinoma↗
PubMed1977

Fc receptors on mouse effector cells mediating natural cytotoxicity against tumor cells.

Mouse effector cells mediating natural cytotoxicity against tumor cells have been previously thought to be lymphocytes that lack any detectable cell surface markers. The present study presents evidence for receptors for the Fc portion of IgG on these cells. By adsorption of cytotoxic spleen cells on monolayers of sheep erythrocytes (E) plus IgG antibodies to sheep erythrocytes (EA), 50 to 96% of the total cytotoxic reactivity could be removed. Parallel adsorption of cells on E monolayers or on EA monolayers coated with protein A, to block the Fc portion of IgG, resulted in little or no depletion of cytotoxic activity. The presence of Fc receptors on the NK cells was confirmed by combining EA rosette formation with velocity sedimentation at unit gravity. Peak cytotoxicity occurred at the same sedimentation velocity as the peak of Fc-positive cells. After EA rosette formation, there was a shift to a higher sedimentation velocity in the Fc-positive cells and in the natural cytotoxic activity. The increase in sedimentation velocity of NK activity that was observed in these experiments indicated that most of the cells had only bound a small number (three or four) of antibody-coated erythrocytes. Together, these data indicate that cells with Fc receptors account for most of the total lytic activity of normal mouse spleen cells.

Animals↗
PubMed1976

Host immune potentiation of drug responses to a murine mammary adenocarcinoma. II. Effect of melphalan therapy on the host immune system.

The role of chemotherapy in influencing tumor-specific immunity to a mouse mammary adenocarcinoma was investigated. By studying different stages of tumor growth we were able to identify several factors important to drug-induced tumor regression: (1) antibody response, (2) delayed hypersensitivity, (3) sensitivity of tumor cells to immune attack and (4) tumor burden. The presence of tumor-specific delayed hypersensitivity and circulating antibody as well as specifically armed monocytes in the tumor mass characterize the T1699 adenocarcinoma. Successful chemotherapy had previously been shown to depend on prior establishment of the above immune responses. Treatment with alkylating agents was marked in all animals by abrogation of a humoral response to the tumor when drug was given early (day 7), and was associated with poor chemotherapeutic results. Later treatment (day 10) was associated with depression of antibody titers only in the minority of animals not responding to drug and prolongation of the delayed hypersensitivity response in all treated animals. Tumors recurring following initial drug-induced regression were marked by lack of delayed hypersensitivity in the host, lack of drug response and suppression of humoral immunity following treatment. Successive passage of cells from these resistant tumors led to decreasing sensitivity to chemotherapy despite established immunity on the part of the host. The selection of tumor cells resistant to immune destruction rather than drug resistance per se appeared to pay a role. Melphalan was thus able to affect both favorably and adversely the immune factors important to drug-induced regression.

Adenocarcinoma↗
PubMed1976

Two functionally distinct anti-tumor effector cells isolated from primary murine sarcoma virus-induced tumors.

The ability of cells from primary MSV-induced tumors to function as effector cells in vitro was evaluated. Host cells were isolated by enzymatic disaggregation of the tumor and fractionated by sedimentation velocity at unit gravity on a Ficoll gradient. Characterization of these cells indicated that 30 to 40 % were T lymphocytes, about 50% were macrophages and less than 5% were B lymphocytes. Two different functional activities were mediated by these cells: cytolysis, as measured by the CRA, and inhibition of proliferation, as measured by the GIA. The effector cells in the CRA were T cells with sedimentation velocities of 3.5 to 4.0 mm/hr, whereas those cells which mediated the GIA were presumably macrophages and displayed a heterogeneity in size two peak sedimentation velocities, one at 4.0 mm/hr and another at 6.0 mm/hr. Activity by the effector cells in the CRA was antigen specific in contrast to the activity in the GIA which was directed against cells which did not carry detectable cross-reacting antigens.

Animals↗
PubMed1976

Possible evidence for antibody-dependent macrophage-mediated cytotoxicity directed against murine adenocarcinoma cells in vivo.

A macrophage-mediated antibody-dependent cellular cytotoxic reaction has been described in a syngeneic murine mammary adenocarcinoma model. The antibody appears to be present in two forms, one apparently complexed with antigen and the other identified as 7S immunoglobulin on Sephadex G-200 and as the IgG2a subclass by blocking of Fc receptors on the macrophages. This antibody is first detected in mice with regressing tumors. Tumor cells from immune mice appear to be coated with this antibody, as they are sensitive to the effects of normal macrophages in vitro, whereas tumor cells from immunologically compromised mice are not. Thus, a macrophage-dependent reaction probably is relevant in the in situ immune defenses against this tumor.

Adenocarcinoma↗
PubMed1975

Host responses within solid tumors: non-thymus-derived specific cytotoxic cells within a murine mammary adenocarcinoma.

The nature of host-derived, specifically cytotoxic cells infiltrating solid murine mammary adenocarcinomas (line T1699) was investigated. Cell suspensions obtained from enzymatically dispersed tumors were separated by sedimentation velocity. The host cell fraction was heterogeneous and contained T-lymphocytes, non-phagocytic cells bearing Fc receptors, eosinophils and monocytes. Host cells equivalent in size to small lymphocytes and bearing Fc receptors were found to be the predominant cell type responsible for colony inhibition. These colony-inhibiting cells were insensitive to lysis with either anti-theta or anti-IgG serum and complement; and they were specific both in their induction and in their mediation and in their mediation of cytotoxicity. Host cells made up the predominant population in spontaneously regressive tumors but only a minor component in progressive tumors, and they were totally absent from progressive tumors in X-irradiated animals.

Adenocarcinoma↗
PubMed1975

Rosette-forming ability of thymus-derived lymphocytes in cell-mediated immunity. I. Delayed hypersensitivity and in vitro cytotoxicity.

Effector cells in delayed hypersensitivity and in vitro cytotoxicity were studied in lymph node cells from animals immunized with sheep erythrocytes (SRBC) in complete Freund's adjuvant. Delayed hypersensitivity response (DHR) was assayed by the increase in foot pad swelling after the intrafoot pad injection of immune cells plus antigen. Cell-mediated cytotoxicity against SRBC was assayed by a microcytotoxicity test with sheep fibroblasts as target cells. Effector cells were antigen specific, sensitive to anti-theta serum plus complement (C), and insensitive to anti-Ig serum plus C. A nonrosette-forming (non-RFC) small lymphocyte effector T cell and a rosette-forming medium lymphocyte effector T cell were isolated by velocity sedimentation. The small lymphocyte non-RFC required a longer time than the medium lymphocyte RFC effector cell to produce maximum activity. Buoyant density failed to distinguish medium lymphocyte effector cells in DHR and in vitro cytotoxicity.

Animals↗
PubMed1975

Rosette-forming ability of thymus-derived lymphocytes in humoral and cell-mediated immunity. II. Helper cell activity.

The technique of velocity sedimentation at unit gravity was used to determine the size and rosette-forming ability of helper cells in nonimmune and immune C57BL/6 mice. Helper T cells were assayed by the ability to cooperate with bone barrow (B) cells in the antibody response to sheep erythrocytes (SRBC) in vivo. 19S helper cells in nonimmune animals were nonrosette-forming small lymphocytes; after immunization with SRBC in complete Freund's adjuvant, 19S helper cells were nonrosette-forming medium lymphocytes. 7S helper cells in immune animals were small lymphocytes which did not form rosettes. No SRBC binding by helper cells was observed under the conditions of rosette formation used.

Animals↗
PubMed1975

Host responses with solid tumors. I. Monocytic effector cells within rat sarcomas.

Morphologic studies of two unrelated progressively growing sarcomas in rats revealed the presence of a large proportion of host cells distinct from tumor cells. Enzymatically or mechanically dispersed tumor suspensions were fractionated by the velocity sedimentation method, which resulted in a separation of host and tumor cells. The host cells had the typical morphology of macrophages and also were adherent to a plastic surface after a short incubation period. The proportion of host cells was greater in a young (10 or 12 days) than in an older tumor (35 days). These macrophage-like host cells isolated from sarcomas 12 and 35 days after implantation inhibited the colony formation of tumor cells in vitro in the nonspecific manner ascribed to activated marcrophages. In addition to these effector cells, the host fraction contained macrophage precursors able to proliferate in vitro but apparently inhibited by the presence of tumor cells. The results indicated that these macrophage-like effector cells may be the predominant host reaction within some rat sarcomas, and also that thymus- and bone marrow-derived lymphocytes act only indirectly if they are involved.

Animals↗