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S Dray

Publications and source records attributed to S Dray.

At least 55 records · Page 3Linked to original sources
PubMed1982

Role of antitumor immunity in cyclophosphamide-induced rejection of subcutaneous nonpalpable MOPC-315 tumors.

Previously, we had reported that a single i.p. injection of 15 mg cyclophosphamide (CY) per kg cured most mice bearing large MOPC-315 tumors (20 to 25 mm; Day 12 to Day 16 tumors) but rarely cured mice bearing nonpalpable tumors (Day 4 tumors). Also, mice that were not cured if treated with CY, 15 mg/kg, when they had nonpalpable tumors could not be cured if treated again with CY, 15 mg/kg, when they had large tumors (14). Here, we show that CY therapy with 15 mg/kg at early stages of tumor growth did not lead to alteration in the biology of the tumor so as to cause an increased resistance to CY-tumoricidal effects, increased resistance to immune lysis, and/or decreased immunogenicity. Treatment of nonpalpable tumor bearers with CY, 15 mg/kg, prior to in vitro immunization of their spleen cells did not reduce the ability of the spleen cells to generate antitumor cytotoxicity in vitro. However, the level of antitumor cytotoxicity generated was lower than that exhibited by in vitro-immunized spleen cells from mice treated with CY, 15 mg/kg, when they had large tumors. With CY, 15 mg/kg, mice bearing nonpalpable tumors could be cured in two ways: (a) by treating a mouse bearing a nonpalpable tumor in the presence of a contralateral large tumor; (b) by adoptive transfer of immune spleen cells given 1 day post-CY therapy. Both procedures resulted in higher levels of antitumor immunity which was apparently responsible for the cure of the mice in cooperation with CY. Thus, the ineffectiveness of CY therapy with 15 mg/kg at early stages of tumor growth correlated with the presence of relatively low levels of host antitumor immunity.

Animals↗
PubMed1981

Genetic control of the expression of allelic Ig genes at the VH a locus in a1/a2 heterozygous rabbits.

Heterozygous rabbits representing 9 of 15 possible a1 and a2 heavy chain haplotype gene combinations among rabbits in the University of Illinois colony were analyzed for ratios of a1 to a2 in serum immunoglobulin (Ig). The Ig from rabbits of the a1x-y-n81f73g74de12,15 heavy chain haplotype in combination with any of three a2-associated heavy chain haplotypes have higher ratios of a1 to a2 than Ig from rabbits in which a1 is encoded by 4 other heavy haplotypes. For example, the mean a1:a2 ratio for adult a1x-y-n81f73g74de12,15/a2x32y33,- n82,f71g75de12,15 rabbits was 12:1 compared to 5:1 for a1x-y33,30n83,f71g75de12,15/a2x32y33,- n82,f71g75de12,15 heterozygous rabbits. Family studies indicated that the a1:a2 ratio was under the control of the heavy chain chromosomal region or a locus closely linked to it. Whether the regulation is due to varying numbers of VH genes and/or J gene segments, a separate regulator gene, or more efficient joining of certain gene segments, has yet to be determined.

Alleles↗
PubMed1981

An alpha2-macroglobulin associated factor produced by T lymphocytes which provides polyclonal stimulation of B lymphocytes to maintain the turnover of their surface Ig.

The supernatant of 'crowded' but not 'spread' rabbit spleen cell cultures contains a macroglobulin factor which behaves in an Ig-turnover assay as any T-independent antigen or polyclonal B-cell activator (PBA). In the supernatants of crowded rabbit lymphoid cell cultures prepared in serum free medium, the factor was found to be associated entirely with the alpha-macroglobulin (alpha M) fraction (alpha 1 + alpha 2). This alpha M was most probably actively secreted by the lymphocytes because: (i) sequential supernatants obtained in serum free medium of crowded cultures contained equal amounts of alpha M as well as equal PBA activity; (ii) the alpha M became labelled when the cells were grown in medium containing a radioactive amino acid. Macrophages were not required for the production of PBA. PBA was not produced when either crowded B or T cells were cultured alone but only when they were cultured together. Purified T cells were not triggered by any plant lectin to produce PBA. By use of anti-alpha 2M allotype antibodies and B and T cells from different rabbits, the PBA was shown to have the allotype of the T-cell donor. The PBA was associated with rabbit alpha 2M but not alpha 1M. We concluded that upon close contact, B cells stimulate T cells to produce a PBA associated with alpha 2M.

Animals↗
PubMed1981

Cooperation between cyclophosphamide tumoricidal activity and host antitumor immunity in the cure of mice bearing large MOPC-315 tumors.

A single i.p. injection of cyclophosphamide (CY), 15 mg/kg, was shown previously to be curative if administered to BALB/c mice 10 to 16 days post-MOPC-315 tumor inoculation when the tumors reached 20 to 25 mm (large tumors) but not if administered to mice four days post-tumor inoculation when their tumors were nonpalpable. Here we show that the curative effect of CY, 15 mg/kg, for mice bearing large tumors was not due solely to the tumoricidal activity of the drug, because three or four days after therapy, when the CY had been cleared from the circulation, viable proliferative tumor cells were present in the primary s.c. tumor site. During tumor regression, the tumors became heavily infiltrated by mononuclear cells. Following therapy, mice bearing large tumors exhibited an active antitumor response, as illustrated by their ability to reject a tumor challenge with 350-fold the minimum lethal tumor dose given as early as 24 hr posttherapy. That the curative effect of CY, 15 mg/kg, for mice bearing large tumors required the presence of T-cell-dependent antitumor immunity (cellular and/or humoral), was indicated by the fact that tumor regression was abrogated by treatment of the tumor bearers with anti-thymocyte serum. Thus, CY drug tumoricidal activity and host antitumor immunity cooperated in the eradication of large MOPC-315 tumors.

Animals↗
PubMed1980

Idiotypic specificities which arise naturally in rabbits following allotype suppression of the major VH subgroup.

In contrast to normal IgG, some of the IgG molecules, which appear in compensation as a result of allotype suppression of IgG molecules of the major VH subgroup (a locus), were found to have an easily identifiable idiotypic specificity. For each of three donors' IgG, a different idiotypic specificity was present, and each idiotypic specificity was found on the Fab, as expected, but not on the Fc fragments. Further analysis of the IgG of one donor revealed that the idiotypic specificity was present on 15% of the Fab gamma fragments. The idiotypic specificity was expressed on IgG which also bor an allotypic specificity of the y locus VH subgroup of IgG which comprised most (72%) of the total compensatory IgG. This suggests that suppression of clones synthesizing the a locus major VH subgroup results in compensation by minor VH subgroup clones more limited in variability. These clones may then proliferate to synthesize larger amounts of IgG bearing the same idiotypic specificity which thereby becomes more easily detectable by immunization of rabbits.

Animals↗
PubMed1980

Opposite effects of different strains or batches of same strain of BCG on in vitro generation of syngeneic and allogeneic antitumor cytotoxicity.

Pretreatment of mice with three batches of BCG Phipps strain 10 days before in vitro immunization of their spleen cells with syngeneic or allogeneic tumor cells augmented the levels of antitumor cytotoxicity (compared to the levels exhibited by in vitro immunized spleen cells from normal mice), whereas pretreatment with another batch of BCG Phipps strain or with a batch of BCG Tice strain suppressed antitumor cytotoxicity. The suppressive effects of these BCG vaccines could not be attributed to route of administration, dose of BCG, or percentage of colony-forming units in an inoculum. The effect of the interval between BCG pretreatment and in vitro immunization on the generation of antitumor cytotoxicity was evaluated; one BCG batch was of special interest, inasmuch as augmented cytotoxicity was obtained when the interval was short and suppressed cytotoxicity was obtained when the interval was long.

Animals↗
PubMed1980

Effect of polyethylene glycol 6000 on the generation of antitumor cytotoxicity in MOPC-315 tumor bearer spleen cells cultured in the presence or absence of inactivated stimulator tumor cells.

Noncytotoxic spleen cells from BALB/c mice bearing 15- to 26-mm (but not 29-mm) s.c. MOPC-315 tumors that were cultured in medium containing 2% polyethylene glycol 6000 (PEG) developed substantial levels of anti-MOPC-315 cytotoxicity as assayed by 51Cr release. The level of cytotoxicity obtained increased with progression of tumor growth. Addition of mitomycin C-treated stimulator tumor cells and PEG to the culture of tumor bearer spleen cells resulted in augmentation of antitumor cytotoxicity to a level that was greater than the sum of the levels of cytotoxicity exhibited by spleen cells cultured in the presence of either mitomycin C-treated tumor cells or PEG. Maximal levels developed when the spleen cells were cultured for 5 to 6 days in 2% PEG at a responder/stimulator cell ratio of 15/1 or 30/1. Tumor bearer spleen cells that were cultured in PEG with or without added MOPC-315 stimulator cells exhibited strong anti-MOPC-315 cytotoxicity but were virtually noncytotoxic to allogeneic EL4 and syngeneic blast cells. Furthermore, these spleen cells were far superior to spleen cells cultured without PEG in mediating in in vivo antitumor activity in the local adoptive transfer assay. Thus, tumor bearer spleen cells cultured in the presence of PEG might be useful in immunotherapeutic regimens requiring histocompatible cells with augmented antitumor cytotoxicity but devoid of reactivity against normal cells.

Animals↗
PubMed1979

Some perspectives on the transfer of cell-mediated immunity by immune-RNA.

Ribonucleic acid extracts of lymphoid cells from immune hosts were used to transfer in vivo and in vitro cell-mediated immune reactivity to a variety of antigens. The in vivo immune responses transferred by RNA included the delayed cutaneous hypersensitivity reaction to fungal and chemically-defined antigens and the tumor-rejection reaction to guinea pig hepatoma antigens. The in vitro immune responses transferred by RNA included macrophage migration inhibition by fungal, chemically-defined, and tumor antigens. The transfer activity of RNA preparations was contained in the 8 s to 18 s species of RNA and was sensitive to RNase but not to DNase or trypsin. Antigen was not detectable in the RNA preparations and appeared to have no role in the transfer activity. Syngeneic, allogeneic, or xenogeneic sources of RNA could transfer immune reactivity. In each system tested, the transfer of cell-mediated reactivity by RNA was specific for the antigen used to sensitize the RNA donor. The potential use of RNA-mediated transfer of immunity is discussed.

Animals↗
PubMed1979

Kinetics of escape from suppression of Ig heavy chain allotypes in multiheterozygous rabbits.

Three rabbits of genotype a1n81f73g74/a2n82f71g75 which had been injected at birth with anti-a l (VH) antiserum and which were previously shown to be suppressed for the paternal allotypes a 1, n81, f73 and g74 at 8 weeks of age, were monitored over a 2-year period for the concentration of suppressed and nonsuppressed allotypes in their sera. In all three suppressed animals, the f73 (C alpha) and g 74 (C alpha) allotypes were expressed again at a much greater rate than the a1 (VH) and n81 (C mu) allotypes. In one suppressed animal, the a l (VH) allotype was re-expressed at a much greater rate than the n81 (C mu) allotype and reflected primarily the reappearance of a l IgG. Thus, the escape from allotype suppression in this animal was in the order IgA, IgG, IgM which is the reverse of the order of appearance of these Ig classes during ontogeny. While the al(VH) and n81 (C mu) allotyes remained suppressed, the f73 (C alpha) and g74 (C alpha) allotypes were re-expressed to the same concentration as in the unsuppressed controls, and no compensatory decrease of the f71 and g75 allotypes occurred. During the re-expression of the f73 and g74 allotypes, the ratio of the concentrations of f73/g74 remained approximately constant.

Animals↗