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J H Coggin

Publications and source records attributed to J H Coggin.

At least 19 recordsLinked to original sources
PubMed1995

CD8 T cell clones inhibit antitumor T cell function by secreting IL-10.

We have reported that in irradiated, long-term surviving RFM strain of mice there is enhanced kinetics of tumor development upon challenge with RFM lymphoma cells. We reported that we cloned splenic oncofetal (OFA)-specific, noncytotoxic CD8+ T cells from such mice. These noncytotoxic CD8+ T cell clones secrete a factor upon Ag stimulation that inhibits the ability of OFA-specific RFM cytotoxic T (TC) cell clones from killing 5T RFM lymphoma cells in vitro. These supernatants do not inhibit the tumor cell-induced proliferation of the TC cell clones however. We report here that OFA-stimulated, RFM-noncytotoxic CD8 T cell clone culture supernatants also inhibit IFN-gamma-secretion by stimulated CD4 and CD8 RFM anti-OFA effector T cell clones in a dose-dependent manner. The inhibitor in those culture supernatants acts in neither an Ag-specific nor MHC-restricted manner. We find that the culture supernatants of OFA-stimulated, noncytotoxic CD8 T cell clones contain IL-10, while those from OFA-stimulated, RFM OFA-specific TC cell clones do not. We show that monoclonal anti-IL-10 Ab specifically blocks the inhibition of cytotoxic activity and IFN-gamma secretion by OFA-specific CD8 and CD4 effector T cell clones in a dose-dependent manner in vitro. Incorporation of anti-IL-10 Ab into the cytotoxicity assays of the OFA-specific, noncytotoxic CD8+ T cell clones against 5T tumor cells restores their cytotoxic activity. This may suggest that one way of inducing anergic T cells is by induction of IL-10 secretion.

Animals↗
PubMed1995

Characterization of RFM mouse T lymphocyte anti-oncofetal antigen immunity in apparent tumor-free, long-term survivors of sublethal X-irradiation by limiting dilution T lymphocyte cloning.

Fractionated sublethal x-irradiation induces thymic lymphomas in up to 60% of RFM mice by 6 mo after irradiation, but no thymomas arise after 6 mo. All radiation-induced tumors expressed oncofetal Ag (OFA) and thymic OFA expression significantly preceded detectable thymomas. To determine whether lymphoma-free, radiation survivor mice had anti-OFA T cell immunity, we analyzed their clonable 5T lymphoma-reactive T lymphocytes and determined the resistance of such mice to challenge with RFM lymphoma cells. RFM mice that were irradiated 6 to 6.5 mo earlier, but which had no apparent tumors, had no more resistance to OFA+ 5T lymphoma cell challenge than nonirradiated age-matched mice. These mice actually developed maximal tumor incidence significantly faster. Analyses of 5T lymphoma-reactive T cell clones established from RFM mice 11 mo after irradiation, however, suggest that activation of anti-OFA immunity occurred subsequent to irradiation. Previously irradiated RFM mice yielded 257% more tumor-reactive T cell clones/mouse than non-irradiated controls. All clones from both sets of mice specifically proliferated to purified OFA. Each irradiated mouse yielded some clones that proliferated to fivefold lower doses of OFA than did any T cell clones from nonirradiated mice. Only these low-dose OFA-reactive clones responded equally to irradiated 4T and 5T cells by proliferation, IFN-gamma secretion, and target lymphoma cell killing. 4T cells express less OFA/cell than 5T cells. Some noncytotoxic CD8 T cells that inhibited cytotoxic T cell function were cloned only from irradiated RFM mice.

Animals↗
PubMed1994

Differential recognition of murine tumor-associated oncofetal transplantation antigen and individually specific tumor transplantation antigens by syngeneic cloned BALB/c and RFM mouse T cells.

We have previously demonstrated in several species that sarcomas, lymphomas, and carcinomas express a common Ag that cross-reacts with midgestation fetal cells. We also produced a mAb to that protein and characterized it as a 44-kDa glycoprotein. The cross-reactive immunity induced by immunization with tumor or fetal cells expressing the oncofetal Ag (OFA) can be adoptively transferred with cell populations containing T lymphocytes. The experiments discussed within this paper describe the establishment and characterization of two types of T lymphocytes induced by immunization with syngeneic tumor cells in two mouse strains. We find that five of the eight cloned T cells derived from spleens of BALB/c mice that had been immunized with MCA1315 fibrosarcoma cells are specific for an Ag shared by MCA1315 and MCA1321 cells. The other three clones are specific for an Ag present on MCA1315 but not on MCA1321. Also, none of the clones were reactive with the BALB/c plasmacytoma MOPC-315, which does not express OFA. We also find that 75% of the RFM T cell clones from spleens of RFM mice immune to the RFM thymoma 5T show a 5T-specific proliferative response. One of the four clones, however, responds to both 4T and 5T RFM thymoma cells. The BALB/c and RFM cross-reactive clones specifically respond to purified 44-kDa OFA derived from MCA1315 fibrosarcoma cells in the presence of syngeneic irradiated spleen cells and IL-2. All of the clones from both strains of mice, be they tumor-specific transplantation Ag specific or OFA specific, are CD4+, CD3+, alpha beta TCR+ T cells that secrete IFN-gamma on Ag stimulation.

Animals↗
PubMed1994

Increased oxygen tensions influence subset composition of the cellular immune system in aged mice.

In acute and chronic experiments, each of eight groups of aged mice were assigned separately to different pressures of oxygen to which it was to be exposed. Lymphocytes from spleen, thymus, and peripheral blood were analyzed following oxygen exposure. Subset populations changed depending on the oxygen tension. Variable changes were observed in total numbers of lymphocytes, lymphocyte subsets, B cells, and macrophages depending on the organ studied and the oxygen pressure to which the mice were exposed. There were differences between acute and chronic exposure suggestive of adaptation to environmental stressors. The suggestion is made that the immune system has a reserve capacity that can be influenced by oxygen and, thereby, theoretically capable of being pharmacologically manipulated to assist patients with altered immune systems to promote defense mechanisms or, under certain circumstances, reduce autoimmunity. It is hypothesized that an underlying hypoxia may be involved in the age-associated decline in the immune system.

Adaptation, Physiological↗
PubMed1993

Increased oxygen tensions modulate the cellular composition of the adaptive immune system in BALB/c mice.

In acute and chronic experiments, each of eight groups of young mice were assigned separately to different pressures of oxygen to which it was to be exposed. Lymphocytes from spleen, thymus, and peripheral blood were analyzed following oxygen exposure. Subset populations changed depending on the oxygen tension. Blood lymphocyte populations reflected lymphocyte changes in thymus or spleen. Thus, a full understanding of the pharmacological effects of hyperbaric oxygen, requires a knowledge of simultaneous effects of increased oxygen pressures on the various compartments comprising the immune system.

Animals↗
PubMed1992

Expression of 44-kilodalton oncofetal antigen as a premalignancy marker in X irradiation-induced murine T-cell lymphoma.

BACKGROUND: Oncofetal antigens (OFAs) are found on the surface of murine and human midgestation fetal cells, in human and rodent tumor tissues, and on human and rodent tumor and embryonic cell lines but not in normal neonatal or adult human and rodent tissue. PURPOSE: The usefulness of OFA as an early indicator of lymphoma development was evaluated. METHODS: With the use of monoclonal antibody directed against a 44-kd glycoprotein, cells from the thymus and spleen of RFM/UnCr mice receiving whole-body, split-dose x irradiation (1.75 Gy once a week for 4 weeks) or cells from these organs from control (nonirradiated) mice were analyzed for the presence of OFA in the flow cytometer and in limited intrathymic transplant. RESULTS: OFA was detected on thymocytes from 75% of irradiated mice by 2 months after treatment, reflecting eventual lymphoma development in the irradiated controls by flow cytometry and in intrathymic transplant. In general, the number of thymuses expressing OFA and the percentage of OFA+ cells increased with time after irradiation. By 4 months, OFA+ splenocytes were present, but only in mice possessing OFA+ thymocytes. Serially tested, irradiated RFM mice that never expressed OFA in the thymus reflected the percentage of irradiated RFM/UnCr mice that never developed lymphomas. This observation was also made in irradiated C57BL/6N mice, which attests to the tumor specificity of OFA expression. Spleen immunoglobulin-positive cells were decreased, while CD4+ and CD8+ cells were greatly increased. Indirect evidence of CD4/CD8 expression on OFA+ splenocytes suggests that the newly forming lymphomas were of immature T-cell origin. Major histocompatibility antigen expression did not vary significantly. Histopathologic examination revealed radiation-induced lymphomas in OFA-positive tissues characterized by a monomorphic population of large blastic immature lymphoid cells. CONCLUSION: The early expression of OFA in radiation-induced oncogenesis was established. IMPLICATIONS: OFA expression significantly preceded clear histologic evidence of malignant T cells or clinical lymphoma in irradiated RFM/UnCr mice that went on to develop T-cell lymphomas.

Animals↗
PubMed1991

Isolation and partial characterization of a soluble oncofetal antigen from murine and human amniotic fluids.

A soluble (cell-free) oncofetal antigen (OFA) was detected in murine and human amniotic fluids by immunostaining with the murine monoclonal antibody (MAb 115) produced by syngeneic immunization with mid-gestational mouse fetal cells. OFA was purified from the amniotic fluids by ammonium sulfate precipitation at 30-70% saturation, followed by successive gel chromatography of the OFA-containing fraction on Sephacryl-S300 HR, Q- and S-Sepharoses and lentil lectin agarose. The fraction eluted from the lentil lectin column gave a single band on SDS-PAGE of the same molecular weight as the membrane-bound OFA found on both fetal and tumor tissues of humans and several rodents. Both soluble and membrane-bound OFAs share several chemical characteristics, including binding to lentil lectin and wheat-germ agglutinin, molecular weight (44 kDa) and pI (6.8). Mild periodate oxidation of OFA did not affect its binding to MAb 115 in an enzyme-linked immunosorbent assay, indicating that the reactive epitope is a peptide.

Amniotic Fluid↗
PubMed1990

Differential expression of class I major histocompatibility complex determinants by lymphoblastic leukemia-lymphoma cell lines.

Two T-cell lines (XR11-4T and XR11-5T), established from radiation-induced, murine lymphoblastic lymphomas, were examined for the expression of class I major histocompatibility complex antigen and tumor induction. These cell lines expressed class I private determinants, H-2.9 and H-2.26, but not the monomorphic determinant defined by monoclonal antibody M1/42. Both cell lines produced tumors in syngeneic and allogeneic hosts. The monomorphic determinant could be demonstrated on both cell lines following growth in allogeneic (BALB/c mice) but not in syngeneic (RFM mice) hosts. The re-expressed determinant present on cells following growth in allogeneic mice was not of host origin. Thus, tumorigenic x irradiation may differentially affect the expression of class I major histocompatibility complex determinants.

Animals↗
PubMed1989

Immunogenicity of a soluble partially purified oncofetal antigen from murine fibrosarcoma in syngeneic mice.

A tumor/fetal associated antigen, termed oncofetal antigen (OFA), conserved in the tumor and fetal tissue of rodents and humans, was extracted from murine fibrosarcoma cells and tumors and was fractionated on an Ultrogel AcA34 gel filtration column. A monoclonal antibody 115 specific for the OFA identified three peaks of antigenic activity in the eluted fractions, designated fractions (Fr.) I, II, and III, in the molecular weight range of greater than 160, 90, and 44 kDa, respectively. Most of the activity resided in the high molecular weight fraction, Fr. I. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis and gel scanning of Fr. I showed multiple bands, one of which, constituting about 5.6% of the total protein bands in Fr. I, was the 44 kDa oncofetal antigen, apparently present in this fraction in a soluble complex form. Lectin binding studies and isoelectric focusing showed that the 44 kDa OFA is a glycoprotein, whose pI is 6.8. Spleen and peritoneal exudate cells of BALB/c mice immunized with Fr. I protected naive syngeneic mice, in adoptive transfer experiments, from developing tumors when challenged with syngeneic fibrosarcoma tumor cells, MCA-1315. Also, immune spleen cells were cytotoxic to the tumor target cells, MCA-1315, in a 51Cr release assay at several different effector to target cell ratios. This is the first description of a conserved, true, oncofetal antigen capable of inducing tumor transplantation resistance in syngeneic rodents in a semipurified form.

Animals↗
PubMed1989

Tumorigenic sublethal whole-body X-irradiation of RFM mice enhances cell-mediated cytotoxicity while transiently depressing T- and B-lymphocytes.

The immunocyte composition of spleens and peritoneal exudates (PEC) from RFM mice was examined following tumorigenic doses of whole-body, sublethal X-irradiation. T-cells, B-cells and macrophages were quantitated using mAb and flow cytometry. The cell mediated cytotoxicity (CMC) potential of PEC following immunization with allogeneic tumor cells was also assayed. Although the percentages of T- and B-cells were depressed in irradiated mice, the CMC activity of PEC from these same mice was increased. Thus irradiation resulted in an increased incidence of tumors coincident with an increased CMC potential against tumor targets.

Animals↗
PubMed1989

Cross-reacting tumor associated transplantation antigen on primary 3-methylcholanthrene-induced BALB/c sarcomas.

Immunization of adult, syngeneic BALB/c mice with irradiated, primary MCA-induced sarcomas conferred reproducible, nonisologous TATA-associated cross-protection against challenge with other primary MCA sarcomas or in vitro passaged MCA sarcoma cells. Isologous, individually specific TSTA-associated protection was also detected. Irradiated, normal BALB/c spleen or muscle tissues were not similarly protective. Pronounced cross-protection was best detected with secondary cultured, in vitro adapted sarcoma challenge inoculum, which could be accurately standardized. These findings paralleled the good cross-protection reported previously with long-term cultured MCA-induced sarcoma cell lines. OFA was expressed as a TATA on all syngeneic, primary MCA-induced sarcomas tested by syngeneic adoptive transfer experiments and on MuLv-free MCA-induced, syngeneic Meth A sarcoma cells.

Animals↗
PubMed1988

Human squamous cell carcinoma lines express oncofetal 44-kD polypeptide defined by monoclonal antibody to mouse fetus.

Most primary human carcinomas uniformly express an oncofetal epitope which has not been demonstrated previously in established human carcinoma cell lines. We successfully derived several low-passage cell lines of human squamous cell carcinoma (SCC) from head and neck tumors using an in vitro adaptation procedure, characterized these lines, and examined them for expression of a 44-kilodalton (kD) polypeptide (PP) oncofetal antigen (OFA) at the cell surface. Newly established an in vitro-passaged SCC cells retained characteristic microvilli, numerous desmosomes and tonofilaments, abundant rough endoplasmic reticulum, osmophilic keratohyaline granules, and other features of the primary SCC cells. These new cell lines and two long-term, established SCC lines (FaDu and Detroit 562) displayed OFA at the cell surface, as determined by flow cytometry using monoclonal antibody (MoAb) 115. While the FaDu and Detroit 562 lines exhibited aneuploidy during flow cytometric analysis, the new, low-passage SCC lines that we developed remained diploid as were the primary SCC cells from which they were derived. We propose that the expression of a 44-kD OFA is a common feature of human SCC. This marker may prove useful in the detection and treatment of these tumors.

Antibodies, Monoclonal↗
PubMed1988

Radiation-induced lymphoblastic lymphomas/leukemias and sarcomas of mice express conserved, immunogenic 44-kilodalton oncofetal antigen.

X-ray-induced, lymphoblastic, T-cell lymphoma/leukemias from irradiated RF mice were observed to uniformly expressed a 44-kd oncofetal antigen (OFA). The OFA polypeptide was detected by flow cytometry, affinity column SDS-PAGE analysis, and immunoblotting with monoclonal antibody (MAb) 115 prepared against syngeneic mouse fetus. X-ray and ultraviolet (UV) induced murine fibrosarcoma cell lines, used as classic models in radiation biology, were also found to express the OFA, which suggested that the 44-kd OFA was a general transformation marker of tumors. Adult mouse thymocytes and other adult tissues expressed no OFA. The 44-kd polypeptide was located at the surface membrane of the tumors examined. In contrast to other reports, lymphoblastic lymphoma cell lines expressed the OFA as a cross-protective, rather than an individually-specific, tumor-associated transplantation antigen. Pronase treatment removed OFA from the surface of living lymphoma cells, whereas collagenase, neuraminidase, and hyaluronidase did not. The OFA was rapidly reexpressed upon culture of the pronase-treated cells. Taken together, these results suggest that the 44-kd OFA polypeptide described here may provide a useful cell surface marker for future radiation carcinogenesis studies. MAb 115 is a promising reagent for detecting tumor-associated 44-kd OFA, for assessing immunoregulatory perturbations to the OFA caused by radiation damage and for investigating the immunopathology of OFA-associated radiation damage.

Animals↗
PubMed1987

Complete, circular papovavirus genomes in the cells of hamsters exposed to a horizontally transmitted lymphomagenic agent.

Contagious lymphomas were produced in a colony of Syrian golden hamsters by an unknown agent that also caused fatal ulcerative bowel disease (UBD) lesions prior to lymphoma development. A low percentage of these animals developed epitheliomas of the skin independently of the UBD or lymphomas. Previous work has shown that the epitheliomas contain numerous hamster papovavirus (HaPV) particles, whereas lymphomas do not. Cells from both kinds of tumors do contain HaPV DNA sequences, however. In this study, Southern blot hybridization showed that complete, circular HaPV genomes were present in these cells. Complete, circular HaPV genomes also were found in the cells of animals with UBD. Electron microscopy revealed the presence of HaPV particles in UBD lesions. These results, together with previous data, indicate that in the hamster, lymphomas contain complete, circular papovavirus genomes in the absence of virus particles, whereas epitheliomas and UBD lesions contain these genomes in the presence of virus particles.

Animals↗
PubMed1986

The implications of embryonic gene expression in neoplasia.

The discovery that human as well as animal tumors generally expressed oncofetal antigens (OFAs) and that these antigens generate a variety of immune responses in the tumor-bearing host is of potential major significance in tumor biology. The concept of the reexpression of embryonic or fetal antigens (EAs) encoded by DNA, which is silent in adults but is essential in metazoan development, may mesh with the exciting concept of cancer causation. While this scenario is still only speculative, it provides an interesting forum for reviewing the current data concerning the role of OFAs in cancer processes. The literature describing OFAs and their embryonic counterparts, the EAs, in modern tumor and fetal immunobiology has become extensive and, unfortunately, is quite scattered. This article seeks to synthesize this complicated data base into a cogent presentation focusing on the immunological role of EAs and OFAs in fetal survival in utero and in tumor progression and regression, respectively. The immunogenicity and characteristics of the immune responses to EAs and OFAs will be presented and placed in perspective to the rapidly unraveling story of protooncogenes and oncogenes in tumor induction.

Animals↗
PubMed1985

Mouse monoclonal antibody to embryonic antigen: development, cross-reactivity with rodent and human tumors, and preliminary polypeptide characterization.

Hybridomas producing IgM and IgG monoclonal antibodies (MoAb) to embryonic or fetal antigens (EA) were obtained in a completely syngeneic system. Lethally irradiated, 13-day-gestation, C57BL/6N mouse fetal cells or KCI extracts of these fetal cells obtained from primaparous donors were used as immunogens in several regimens to induce splenocytes in C57BL/6N mice that were utilized to form the hybridomas following fusion with a mouse myeloma line. Successful growth and cloning of the IgM-producing hybridomas required supplementation with factor(s) produced in the growth medium of the macrophage cell line RAW 264.7. An enzyme-linked immunosorbent assay (ELISA) was employed to screen the primary fusion hybridomas for antibody directed against fetal cell or adult cell determinants with the use of freshly explanted tissues. Glutaraldehyde-fixed fetal cells as well as crude fetal cell membranes were used as EA+ target cells (i.e., cell lines known to activate T-lymphocyte-mediated tumor resistance) in a solid-phase ELISA to perform quantitative ELISA adsorption tests of the MoAb. The anti-EA monoclonal IgM and the IgG detected common, embryo-specific antigen(s) on mouse, hamster, and human fetuses. Term fetal cells and adult normal tissues of the mouse, hamster, and human did not express cross-reactive determinants for the MoAb by absorption analysis and/or by direct binding in ELISA. EA expression as oncofetal antigens could also be detected with the monoclones on several rodent tumor cell lines tested as well as on a variety of human carcinomas but not on a spectrum of normal human tissues with the use of indirect ELISA absorption and affinity gel and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analyses. Fluorescence analysis with the monoclones demonstrated specific reactivity with the surface of EA+ tumor cells in the FACS IV flow cytometer. The responsible antigen was carried on a 44- and a 200-kilodalton polypeptide.

Animals↗
PubMed1985

Papovavirus in epitheliomas appearing on lymphoma-bearing hamsters: lack of association with horizontally transmitted lymphomas of Syrian hamsters.

Several epizootics of lymphoma occurred in a colony of LVG hamsters contaminated with an unusual, horizontally transmitted, subviral, lymphomagenic agent. Hamsters with horizontally transmitted lymphoma, or others housed with these hamsters, occasionally developed epitheliomas bearing an unclassified papovavirus. The possibility that the virus present in the wart-like structures in our hamster colony could activate lymphoma was tested, and a search was conducted for mature virions in passaged epitheliomas and lymphomas. The agent responsible for the skin epitheliomas in our hamster facility was an icosahedral, 36-nm virion compatible with the morphology of a polyomavirus or simian virus 40. Horizontally transmitted lymphoma cells and epitheliomas contained hamster papovavirus (HaPV) DNA sequences detected by dot hybridization; however, such sequences were not found in extracts of lymphomas with oncogenic potential. In contrast to reports by other investigators, infection of hamsters with the papovavirus present in primary epitheliomas produced epitheliomas in good yield but was not reproducibly associated with lymphoma induction. These data confirm the observation that the HaPV is the causative agent of epitheliomas, but they suggest clearly that HaPV is not the agent responsible for lymphomagenesis.

Animals↗