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Biomedical subjects

R G Kinsky

Publications and source records attributed to R G Kinsky.

At least 37 records · Page 2Linked to original sources
PubMed1982

Passive allograft enhancement by subclasses of polyclonal antibodies directed toward restricted regions of the major histocompatibility complex.

Two parameters of enhancing major histocompatibility complex (MHC) antibodies, previously separately studied, namely, Ig class and antigen specificity, have been treated simultaneously. In the experimental model used, Sa 1 tumor cells, indigenous of A/J (H-2a) were grafted on CBA (H-2k) or C57BL/Ks (H-2d) mice. Immune sera specific for the H-2 K/D- or H-2 I coded antigens of the A/J haplotype (anti-Kk, or IAk, IBk, IJk, IEk, or ICd, Sd, Gd, or Dd) and their immunoglobulin fractions (separated on protein A-Sepharose columns) were injected either i.v. or locally as mixture with the challenging Sa 1 cells. Within the limits of the studied system, the following results were obtained: (1) Sa 1 cells do possess Iak antigens at their surface detected by C-dependent cytotoxicity; no ICd, Sd, or Gd products were detected. (2) The bulk of enhancing activity is concentrated in IgG1 anti-K/D antibodies (anti-Dd when Sa 1 was grafted on CBA mice and anti-Kk, on C57BL/Ks). (3) Anti-Iak antibodies have some activity on Sa 1 cells grafted on C57BL/Ks mice. This activity is significant for IgG1 anti-Iak and suggestive for IgG2 of the same specificity. (4) No enhancing activity was detected in the other antibodies: IgG2 anti-Dd, IgG2 anti-Kk, IgG1, or IgG2 anti-ICd, Sd, Gd as well as in fractions containing IgM and IgA antibodies directed against any studied portion of the MHC products. This results are discussed in terms of the mechanisms involved in enhancement.

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PubMed1978

Ia versus K/D antigens in immunological enhancement of tumor allografts.

The respective role of anti-H-2 K/D and anti-H-2 Ia antibodies in allotransplanted tumor enhancement was tested in vivo on two experimental tumors. Sa I A/4 (H-2a, i.e., H-2k/d) was enhanced in CBA (H-2k) and C57BL/Ks (H-2d) strains with anti-A/J immune sera prepared in CBA and C57BL/Ks, respectively. EL 4, C57BL/6 (H-2b) lymphoma, was enhanced in DBA/2 (H-2d) and BALB/c (H-2d) with immune sera prepared in DBA/2 and BALB/c. Anti-K/D antibodies were obtrained by elution from glutaraldehyde-treated RBC previously incubated with corresponding alloimmune sera prepared in mice immunized with spleen cells, thymocytes, or two consecutive skin grafts syngeneic to the RBC. The residual complement-dependent serocytotoxicity for target lymphocytes observed after complete hemagglutinin absorption on corresponding RBC was attributed to anti-Ia antibodies. RBC eluates (anti-K/D) were found to be enhancing for both experimental tumors and for all studied sera. After RBC absorption, the sera lost all enhancing activity when they were prepared by immunization with spleen or thymus cells, but remained enhancing in some sera prepared by immunization with skin grafts. Both types of antibodies (anti-K/D and anti-Ia) therefore appear able to enhance allografts. These results are compatible with the in vitro correlates of the two phases of the transplantation reaction: initiation phase (mixed lymphocyte reaction) inhibitable by anti-Ia and effector phase (cell-mediated cytotoxicity) inhibitable by anti-K/D.

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PubMed1978

Evaluation of in vitro and in vivo activities of isoantibodies directed against idiotypes and recognition structures for transplantation antigens.

Anti-idiotype sera were prepared by injection of CBA anti-A/JAX serum with or without adjuvant into CBA mice. These sera were tested in allocluster inhibition and passive enhancement-facilitation. While the anti-idiotype sera inhibited allocluster formation, particularly when prepared with complete Freund's adjuvant, they had virtually no effect on enhancement of Sa I grafted in CBA mice except for a marginal prolongation of graft survival in one out of three experiments. Anti-RS serum was prepared by immunizing (CBA X A)F1 mice with CBA thymus or spleen cells. The sera were tested in local graft-versus-host inhibition and passive enhancement. F1 anti-CBA thymus serum inhibited the local graft-versus-host reaction but had no enhancing effect. F1 anti-CBA spleen serum was virtually ineffective in both tests although a slight tendency to graft-versus-host inhibition was noted. The relative contribution of anti-idiotype and/or anti-RS antibodies to transplantation reactions is discussed.

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PubMed1976

The intersex difference in the production of alloantibodies and growth of tumour allografts in mice.

The comparisons of immune responses to tumour allografts in male and female mice showed the following intersex differences: 1. Production of humoral antibodies is, in general, higher in females; since, however, the time course of titres differs for haemagglutinating and cytotoxic antibodies as well as with the sex, the titre of the same antibody may be higher in males at certain time intervals when the peak is delayed and the production in females is already declining. 2. In recipients specifically presensitized with spleen extract as well as in controls, the growth of allogeneic tumour (SaI) exhibits quantitative intersex differences being reduced in females. In the initial phase of growth, following the spleen extract, the facilitation (enhancement) of the tumour allograft is apparent olny in males, whereas in females it is delayed. 3. The facilitating effect of antibodies passively transferred from males or females corresponds mainly to the sex and strain of the recipient, only rarely to the sex of the producer. 4. In CBA strain mice, females are more resistant to the growth of SaI and also mortality from the primary tumour is lower in females; in contrast, the frequency of metastases in females is higher. 5. In the IC strain, where the sex effect on tumour growth is particularly pronounced, the consequences of castration were concordant with the inferred hormonal control of the allograft response: in males, the relatively high percentage of lethal spontaneous takes (60%) was reduced following castration (to 13%), whereas the opposite trend was observed in females, namely an increase from 0% in sham-operated controls to 23% in the castrated group.

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PubMed1975

Biologic properties of transplantation immune sera. IV. Influence of the course of immunization, dilution and complexing to antigen on enhancing activity of Ig classes.

The influence of the course of immunization on the facilitating-enhancing activity of antibody classes has been studied by passive enhancement of growth of A/JAX sarcomas in CBA and IC mice and of C57BL/6 EL 4 leukemia in BALB/c mice. The influence of dilution of antibodies and complexing to antigens was also studied. During immunization (with several boosters), the enhancing capacity of sera increased together with 7S IgG antibody activity, but showed no correlation with 19S IgM antibody activity. It also was mercaptoethanol resistant. IgG1 to be more enhancing than an equal number of hemagglutinating units of IgG2a. When concentrated on a small amount (10(5)) of target sarcoma I cells, complement-fixing IC anti-A antibodies were even inhibitory on Sa I allografted to IC recipients. Progressive dilutions reversed this situation, IgG1 activity disappearing and IgG2 acquiring enhancing activity. After complexing to corresponding antigens IgG2 also (and immune sera with inhibitory properties) acquired enhancing properties. These results may provide a basis for understanding the discrepancies between the results of several groups of authors studying the class(es) of enhancing anibodies.

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PubMed1972

Immune status of mice tolerant of living cells. II. Continuous presence and nature of facilitation-enhancing antibodies in tolerant animals.

CBA mice were rendered highly tolerant to A/Jax cells by neonatal intravenous injections of (CBA x A)F(1) spleen cells. The high degree of tolerance was ascertained by the absence of circulating antibodies detected in the sera by the usual tests and by the perfect state of A skin grafts during all the experiments. Tolerant sera (sera from tolerant animals) were studied at three periods of tolerance: before skin test grafting, from 2 to 11 wk after grafting, and at time of sacrifice at almost 6 months of age. The tolerant sera were shown to have specific facilitation-enhancing properties promoting the take and growth of A/Jax sarcoma (SaI and /Sa 15091a grafted on normal CBA mice. These properties were present throughout the duration of the experiments, showing that they were not the result of a beginning interruption of tolerance. The tolerant sera, although lacking the usual serological properties (hemagglutination, hemolysis, cytotoxicity, passive cutaneous anaphylaxis) had, however, specific synergistic hemagglutinating properties (increasing the hemagglutinating titer of a reference immune serum). Antibodies giving direct specific hemagglutination could be extracted from spleens of 20% of highly tolerant mice. The tolerant sera were also found to contain more IgG1 and more IgA than normal sera while they contained normal quantities of the complement-fixing immunoglobulins IgG2 and IgM. Fractionation of tolerant sera on DEAE chromatography column confirmed the data concerning immunoglobulin classes and demonstrated direct specific serological activities undetected in unfractionated sera: a weak hemolysis in the most cationic fractions and a weak hemagglutination in the middle fractions. Synergistic hemagglutination, detected in unfractionated serum, was localized in fast anionic fractions containing high IgA concentration, along with facilitation-enhancing activity, thus confirming a link suggested previously between these three properties. The relation between immunological tolerance and facilitating antibodies was discussed in the light of the fact that antibodies, possibly of a particular class continuously present at low dose in the sera of highly tolerant animals, are able to transfer (at least partly) this state of tolerance provided a sensitive test system is utilized.

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