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Biomedical subjects

G Parmiani

Publications and source records attributed to G Parmiani.

At least 253 records · Page 14Linked to original sources
PubMed1982

Cross-reactions between tumor cells and allogeneic normal tissues. Inhibition of a syngeneic lymphoma outgrowth in H-2 and non-H-2 alloimmune BALB/c mice.

To test whether alloimmunization with H-2 or/and non-H-2 different normal tissues may increase the immunity to syngeneic tumors, groups of BALB/c (H-2d) mice were immunized with a series of allogeneic lymphoid cells and then challenged i.p. with syngeneic lymphoma cells. The outgrowth of otherwise lethal doses of the Moloney virus-induced lymphoma YC8 and of its clones was inhibited in BALB/c mice immune to DBA/2 (H-2d), C3Hf (H-2k), C3H.SW (H-2b), C3H.OH (H-2o2) and to B10 background tissues but not in mice immunized to A/He, BALB.K (H-2k) or BALB.B (H-2b) normal tissues. Anti-YC8 effect was also induced by immunizing BALB/c recipients with a pool of five different allogeneic cell lines which included C3Hf, C57BL/6J (H-2b), N:NIH (H-2q), B10.M (H-2f), and DBA/2 lymphoid cells. No growth inhibition of other BALB/c lymphomas induced by Moloney virus (LSTRA), X-rays (RL male I) or urethane (UR-1) was evident in alloimmune mice. In vivo transfer of growth inhibition of YC8 was obtained with BALB/c anti-B10.D2 peritoneal exudate cells in a Winn assay. The ability of these alloimmune lymphoid cells to delay significantly the survival time of BALB/c mice injected with the mixture of immune cell and YC8 cells was abrogated by anti-Thy 1.2 plus C' treatment. In addition, nu/nu BALB/c mice were unable to develop resistance to YC8 outgrowth after alloimmunization. The results of this study show that: (1) syngeneic growth of a lymphoma can be prevented by alloimmunization with normal cells; (2) this cross-reaction involved non-H-2 antigens; (3) the phenomenon appeared to be mediated by T cells.

Animals↗
PubMed1982

Immunogenic variants obtained by mutagenesis of mouse mastocytoma P815. V. H-2 associativity of variant-specific antigens.

By in vitro mutagenesis of mastocytoma P815, it is possible to obtain tumor cell variants that are rejected by syngeneic mice (tum-). Most of these variants carry new individual antigens and stimulate a specific cytolytic T cell (CTL) response in mixed leukocyte tumor cell culture (MLTC). The H-2 associativity of this response was examined for six different variants by measuring the inhibition of cell-mediated cytolysis by antibodies directed against products of the K or the D end of the H-2d complex. The lysis was either not inhibited (variants P91 and P116) or inhibited selectively by anti-Kd (variants P21, P32 and P198) or anti-Dd antibodies (variant P35). All these tum- variants expressed Kd and Dd antigens as measured by absorption of H-2 alloantisera. Long-term CTL clones can be obtained that are specific for individual tum- antigens. The pattern of H-2 associativity obtained with MLTC-derived CTL against four tum- variants was verified with CTL clones directed against the specific antigens of these variants. Concordant results were observed in all cases. In addition to CTL clones specific for tum- antigens, it is possible to isolate clones against a P815 tumor-associated antigen found on all P815 tum- variants. For these clones no clear associativity with either Kd or Dd products was found.

Animals↗
PubMed1982

Lysis of autologous human melanoma cells by in vitro allosensitized peripheral blood lymphocytes.

Peripheral blood lymphocytes (PBL) of melanoma patients were sensitized in vitro with lymphocytes of a single donor or with a pool of lymphocytes of 5-20 different donors. After 6-7 days, the cytotoxic activity of the sensitized PBL was tested against cultured autologous tumor cells and lymphocytes in a 51Cr-release assay. Tumor lysis was observed in 13 of 16 cases in which patients' PBL (Pt-PBL) were stimulated by a pool of allogeneic lymphocytes and in five out of seven cases when single sensitization was performed. In no case was lysis of autologous normal lymphocytes or blasts seen. Cultivation of Pt-PBL with irradiated autologous tumor cells never led to the induction of lymphocytes cytotoxic to melanoma cells. Lysability by pool-activated autologous Pt-PBL of fresh cryopreserved tumor cells was compared to that of short-term cultured tumor cells, and no significant differences were observed. Cold-target inhibition experiments indicated that the cytotoxicity of Pt-PBL was tumor-restricted since only autologous melanoma cells but not lymphocytes were able to inhibit the reaction. These results indicate that activation of Pt-PBL is necessary in order to elicit or amplify their antitumor activity.

Cytotoxicity, Immunologic↗
PubMed1982

Biochemical analysis of a public H-2 specificity revealed by an anomalous reaction of an alloantiserum with a chemically induced C57BL/10 fibrosarcoma.

D-25 is a H-2 alloantiserum produced in (B10.D2 X C3H.NB) (H-2d X H-2p)F1 mice after immunization with B10.RIII(H-2r) cells, and which is known to recognize the H-2.25 public antigen on H-2k haplotypes. The "anomalous" reaction of D-25 with a partially purified deoxycholate-solubilized glycoprotein of B10-1 (H-2b) fibrosarcoma was studied with various biochemical techniques. The 125I-labelled precipitates were analysed both in one- and two-dimensional SDS-PAGE and by a partial proteolysis peptide mapping (Cleveland's mapping). The results indicate first that the D-25-related antigen was a genuine H-2 antigen normally associated with the B2-microglobulin, second that this antigen was borne by the Kb but not Db gene products, and finally that D-25 was able to precipitate the same antigen on normal H-2b spleen cells. We conclude that this serum recognized a normal H-2 specificity shared by H-2b and H-2r haplotypes and tentatively identified as the public antigen H-2.54 which for the first time could be assigned to the K but not to the D region of the H-2b haplotype.

Animals↗
PubMed1981

Importance of non-H-2 genes in the control of the in vivo growth of the virus induced lymphoma YC8.

The genetic control of the in vivo growth of the Moloney virus-induced BALB/c lymphoma YC8 was studied in F1 hybrids between BALB/c and several strains differing at the MHC and/or at the level of non-H-2 genes. Parental strains of the B10 and C3Hf but not of A, BALB/c or DBA/2 backgrounds introduced a significant resistance to the growth of 10(2) YC8 cells (a dose able to kill 100% of BALB/c mice) in semisyngeneic hosts. This resistance appeared to be due to non-H-2 genes although a modulation of the tumour growth by genes encoded by the MHC was also evident. The study of backcrosses between susceptible BALB/c and resistant (BALB/C X B10.BR)F1 crosses revealed that 83% of animals developed lethal tumours after injection of 10(2) YC8 cells. This high frequency of tumour takes was not linked to genes of the MHC. Adult thymectomy plus sublethal irradiation was able to abrogate the resistance of (BALB/c x B10.BR) or (BALB/c x B10.RIII)F1 mice to YC8 growth. Since the injection of silica also impaired the resistance to YC8, we tentatively concluded that the genetic control of resistance to YC8 is mediated both by T cells and macrophage-like cells.

Animals↗
PubMed1980

Expression of alien minor histocompatibility antigens distinct from tumor-specific transplantation antigen on a murine fibrosarcoma.

The fibrosarcoma ST2, induced by 3-methylcholanthrene in BALB/c (H-2d) mice, also expressed alien histocompatibility antigens of the C3Hf and B10 background not encoded by the MHC. To examine the relationship between these alien, minor antigens and the tumor-specific transplantation antigen (TSTA) of the tumor, in vivo immunogenicity test were performed in BALB/c mice and in hybrids between BALB/c and C3Hf (H-2k), C3H.OH (H-2o2), C3H.SW (H-2b), BALB.K (H-2k), B10.BR (H-2k), and B10.D2 (H-2d) mice. A significant loss of TSTA immunogenicity was found in (BALB/c x C3Hf) and in (BALB/c x C3H.OH)F1 animals and, to a lesser extent, in (BALB/c x C3H.SW)F1 mice as compared to the immunogenicity of the tumor in BALB/c mice. Immunogenicity tests with ST2 in BALB/c x (BALB/c x C3Hf) or in BALB/c x (BALB/c x B10.D2) backcross mice, respectively, revealed that half of the BALB/c x (BALB/c x C3Hf) and 97% of the BALB/c x (BALB/c x B10.D2) animals were able to mount an immune response to ST2. To see whether the loss of TSTA immunogenicity in (BALB/c x C3Hf) was due to common determinants shared between TSTA and alien non-H-2 C3Hf antigens or to a genetically linked low responsiveness to TSTA introduced by C3Hf and C3H.OH strains, BALB/c mice were immunized with normal tissues of some BALB/c x (BALB/c x C3Hf) backcross, anti-ST2 resistant mice. Normal tissues of anti-ST2 resistant, dd and dk typed backcrosses were able to immunize BALB/c mice against a challenge of an otherwise lethal dose of ST2 cells. Some but not all BALB/c x (BALB/c x B10.D2) anti-ST2 resistant donors had tissues able to immunize BALB/c hosts aginst the ST2 growth. Since resistance to tumor growth and expression of minor "alien" antigens shared with the tumor segregate independently, we concluded that alien, minor C3Hf and B10 antigens of the BALB/c sarcoma ST2 are distinct from the TSTA of this tumor.

Animals↗
PubMed1980

Separation of the tumor-associated transplantation antigen (TATA) from the alien H-2k antigens expressed on a methylcholanthrene-induced tumor.

The tumnor-associated transplantation antigen (TATA), alien H-2k antigens and normal H-2d antigens expressed on a methylcholanthrene-induced tumor were monitored during gel filtration and lectin affinity chromatography of detergent-solubilized tumor-cell membranes. TATA was resolved from both the normal and alien H-2 antigens by these techniques. The relationship between histocompatibility antigens and TATA is discussed.

Animals↗
PubMed1979

Alien H-2 antigens on a chemically induced fibrosarcoma: further evidence in crude membrane and soluble extracts of the tumor.

Crude membranes (CM) were obtained from in vivo subcutaneous nodules of the methylcholanthrene-induced BALB/c fibrosarcoma C-1 by forcing tumor fragments through a mechanical press and subsequent differential centrifugation. This immunogenic tumor has been previously shown to express both H-2d and extra H-2k-like antigens. Original H-2d and alien H-2k antigenic activities were present in CM C-1 as judged by the specific inhibition of the C'-dependent cytotoxicity of monospecific H-2 alloantisera on normal 51Cr-labelled lymphoid cells. Both K- and D-end private H-2d antigens (31 and 4), and H-2d public antigens 8, 29, 35 were detected in CM C-1. In addition, the alien H-2Kk.23 private specificity and the public H-2k.1, 5, and 25 were also found in CM C-1. A weak but reproducible activity attributable to the Dk private antigen 32 was also revealed in this material. A hierarchy in the expression of both H-2d and H-2k specificities was evident in CM C-1 which paralleled, although with an overall lower antigenic activity, those of two other BALB/c (H-2D) FIBROSARCOMAS AND OF A C3Hf (H-2k) lymphoma, respectively. CM from normal BALB/c and C3Hf spleens, while expressing higher amounts of all the tested H-2 antigens, displayed a hierarchy of the different specificities similar to that of neoplastic tissues. Crude soluble (CS) material was obtained from CM C-1 by deoxycholate treatment and was tested in the inhibition assay for the presence of H-2d and alien H-2k antigens. Only specificities with the highest expression in CM were found in CS, i.e. H-2.4 and 29 for H-2d and H-2.25 for H-2k. Both CM and CS from C-1, but not from another control BALB/c sarcoma, were able to significantly inhibit the activity of an oligospecific serum to the Kk-coded antigens.

Animals↗
PubMed1979

Preparation of antigenically active membranes from solid murine lymphomas and fibrosarcomas.

Plasma membrane preparations were obtained from solid lymphosarcomas and fibrosarcomas by disrupting the tissues with a mechanical press. The subcellular fractions were isolated by differential centrifugations and examined by electron microscopy. The membrane-enriched fractions were also assayed for protein content and analyzed in SDS-polyacrylamide gel electrophoresis; a fairly good reproducibiltiy was found comparing different membrane preparations derived from the same tumor. The H-2 antigenic activity of the different membrane preparations was demonstrated in vitro by the inhibition of the C'-dependent 51Cr-release assay using monospecific H-2 alloantisera. The specificity of the assay was ascertained by the lack of inhibition of unrelated monospecific H-2 alloantisera and by a dose-response relationship between the amount of added membranes and the observed inhibition. The immunogenicity of the membranes was assessed in vivo by immunizing allogeneic mice that developed anti-H-2 alloantibodies. The possible mechanisms of the tissue disruption by the press are also discussed.

Animals↗