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Biomedical subjects

R M Gorczynski

Publications and source records attributed to R M Gorczynski.

At least 145 records · Page 8Linked to original sources
PubMed1983

A possible maternal effect in the abnormal hyporesponsiveness to specific alloantigens in offspring born to neonatally tolerant fathers.

Newborn CBA mice were inoculated i.p. with 1 X 10(8) adult (CBA X A)F1 lymphoid cells with 5 X 10(7) F1 hybrid lymphoid cells thereafter inoculated i.v. at 14-day intervals. The mice were subsequently grafted with A/J tail skin at 24 days of age. At 8 wk of age, individual tolerant males with intact skin grafts were each mated with similar tolerant skin-grafted females or with 8-wk-old control normal CBA females. Approximately 0.4 ml of peripheral blood from 7-wk-old progeny born to these crosses, along with the blood from age-matched progeny born to normal CBA incrosses, were used for in vitro mixed leukocyte cultures (MLC). All progeny received skin grafts of (CBA X A)F1 tail skin at 7 1/2 wk of age. In this study, we show i) that MLC hyporesponsiveness to histocompatible cells is an acquired phenotype expressed by lymphoid cells of the progeny of tolerant male mice, and ii) that these progeny also show delayed rejection of (CBA X A)F1 skin grafts. The continued breeding of the first generation animals established that a similar transmission of hyporesponsiveness can be observed in the second generation progeny. When putatively normal females, however, which had borne several litters after mating with neonatally tolerant males, were mated with "normal" (nontolerant) males; their offspring also exhibited a specific hyporesponsiveness in MLC to the initial tolerizing allodeterminants. This suggests that there may ultimately be a maternally derived origin for the transmission of characters from tolerant males.

Animals↗
PubMed1983

In vitro analysis of allogeneic lymphocyte interaction. VI. I-J-restricted self-reactive and alloreactive components of allogeneic effect factor (AEF) are distinct I-J- molecules that interact with I-J+ T cells and antigen-presenting cells.

An allogeneic effect factor (AEF) generated across an I-J incompatibility was derived from MLR cultures of alloactivated B10.A(3R) responder T cells and irradiated T cell-depleted B10.A(5R) stimulator spleen cells. This AEF consists of two soluble, secreted I-J-restricted helper components. One helper component, TH-I, recognizes self-I-J determinants on an I-J+ B10.A(3R) antigen-presenting cell (APC), whereas the other helper component, TH-II, recognizes allo-I-J determinants on an I-J+ B10.A(5R) APC. TH-I-B10.A(3R) APC interaction and TH-II-B10.A(5R) APC interaction each induce an in vitro primary anti-SRBC PFC response of either B10.A(3R) or B10.A(5R) B cells. Thus, I-J determinants serve as restricting elements during a TH-APC and not an APC-B interaction. TH-II mediates the I-J-restricted allogeneic effect required to activate T suppressor (TS) cells during a contact sensitivity or delayed-type hypersensitivity response to hapten-conjugated syngeneic lymphoid cells. This indicates that TH-II is also involved in a TH-pre-TS type interaction. TH-I and TH-II are I-J-, 68,000 m.w. molecules that differ by about 0.10 units in their pl values. Their charge difference is not due to an altered amount of sialylation or phosphorylation, but may result either from another form of altered glycosylation and/or from a difference in their primary structure. Peptide mapping analyses reveal that TH-I and TH-II possess at least 80% shared peptides and may be structurally homologous but nonidentical molecules; however, the possibility that TH-I and TH-II are structurally identical cannot be eliminated. Papain cleaves TH-I and TH-II into a 40,000 m.w. fragment. No subunit structure of TH-I and TH-II is apparent. It is suggested that TH-I and TH-II are I-J- -activated responder T cell-derived receptors for self-I-J and allo-I-J determinants, respectively.

Amino Acid Sequence↗
PubMed1982

Conditioned immune response associated with allogeneic skin grafts in mice.

Groups of CBA mice were given sham skin grafts (conditioned stimulus, CS) or alloantigen only (unconditioned stimulus, US; C57BL/6 lymphoid cells inoculated i.p.). A further group of animals received simultaneous US and CS (alloantigen (US), in this case actually given in the context of a C57BL/6 skin graft). The peripheral blood leukocyte (PBL) pool of all animals was analyzed in tissue culture for the frequency of cytotoxic T lymphocyte precursors (CTLp) specific for alloantigens on the grafted tissue. After three "conditioning" trials, spaced at intervals to allow recovery in all groups of the CTLp frequency to that of naive control mice, individuals in all groups were sham-grafted (given CS alone). PBL of these mice were tested 2 days after removal of the casts. Only group CS + US, and only some 50 to 60% of these, were able to show a "conditioned" increase in the CTLp frequency specific for alloantigens of the grafted tissue after sham-grafting. When these "responder" mice were subdivided into two groups that were subsequently given two trials of CS only or CS + US, followed by retesting with CS alone, either extinction or reinforcement of the previously conditioned response was observed.

Animals↗
PubMed1982

Role of genes in murine major histocompatibility complex (MHC) in the ontogeny of B cells with restricted capacity for cooperation with adherent cells in the production of antibody to thymus-dependent (TD) and thymus-independent type 2 (TI-II) antigens.

We have examined the MHC restriction that exists for cooperation between B lymphocytes and antigen-pulsed accessory cells for antibody responses in tissue culture, using B cells prepared from spleen cell suspensions of progeny born to (B10 x B10.BR)F1 female mice mated with B10 males. At early times post-birth (3 to 6 wk) progeny animals types as H2b contained a population of splenic B cells restricted to MHC antigens expressed on B10.BR macrophages; in contrast, B cells from H2b animals born to the incross (B10 x B10) were as expected, restricted to cooperate only with B10 macrophages. This unusual restriction pattern waned with age such that by 20 wk of age considerably fewer of the B10 progeny born in the backcross mating exhibited this behavior. We interpret these data as evidence that the early B cell repertoire is to some degree 'driven' by exposure to those MHC antigens (in the maternal placental circulation) encountered in utero. Post-birth, continued renewal of the mature B cell pool occurs concomitant with a diversification (and selection) of the B cell repertoire as a result of experience with antigens lacking this maternally imparted genetic information.

Aging↗
PubMed1982

Retardation and promotion of growth of spontaneously appearing tumors using immune lymphocytes previously exposed to embryonic antigens.

Spleen lymphocytes taken from mice at various stages of pregnancy or growth of s.c. syngeneic tumor implants have been examined for their ability to cause cytolysis of embryo fibroblasts in culture or to affect the growth of the transplanted tumor cells in vivo. Activity of different lymphoid populations in affecting tumor growth in vivo was correlated with activity in vitro, whether cytolysis (growth inhibition) or blocking of cytolysis (growth promotion) was considered. The evidence favors an important role for lymphoid responses to embryo-associated antigens in the control of spontaneous tumor growth, although one cannot yet rule out a crucial role for the host milieu rather than, or in addition to, host cellular elements being the important feature of this control process.

Animals↗
PubMed1981

Simultaneous yet independent inheritance of somatically acquired tolerance to two distinct H-2 antigenic haplotype determinants in mice.

We have previously presented evidence that somatically acquired immunological tolerance to foreign histocompatibility antigens induced in male inbred mice can be transmitted at a high frequency to first- and second-generation offspring without exposure of the progeny to the tolerizing antigenic stimulus. These data have in turn been interpreted to support a hypothesis predicting soma to germ-line inheritance for acquired states of the immune system. Formal proof of this genetic scheme at the molecular level is not yet available. However, an even stronger reason for abandoning the notion of the isolation of the germ line from the soma (Weismann's doctrine) would be provided by a clear demonstration of the multiple inheritance of independently acquired somatic characters. Here we present evidence that individual male mice (B10) made tolerant to two different H-2 haplotypes (B10.BR, B10.D2) can transmit the tolerance state to each haplotype independently, yet often simultaneously, at a high frequency to both first and second generation progeny.

Animals↗
PubMed1981

Inhibition of cell proliferation rather than of cell lysis as a measure of immune reactivity in embryo-antigen-challenged mice.

An assay system is described in which effector cells added along with suitable target cells inhibit, in a quantitative fashion, the subsequent uptake of 3H-thymidine by those target cells. Effector cells active in this assay, using embryonic fibroblast cells as targets, develop spontaneously in cultures of mouse lymphoid cells, but are apparently different from those described earlier by investigators of activity in cytotoxic assays. Further evidence is presented to show the development of spleen-derived effector cells with cytostatic activity (for embryonic fibroblast target cells) in mice during the course of normal pregnancy, or growth of spontaneously appearing mammary adenocarcinomas. Indeed, such effector cells can also be found within the growing solid mass itself. Different populations of tumour cells isolated from a solid tumour apparently differ in their susceptibility to growth inhibition by tumour-bearer-derived cytostatic effector cells, a phenomenon which may be related to metastatic spread of tumour cells.

Adenocarcinoma↗
PubMed1981

Tumour-cell susceptibility to cytotoxic or cytostatic effector cells in vitro and the regulation of tumour-cell growth in vivo.

Tumour-cell growth in lung nodules after i.v. transfer to sublethally irradiated mice has been followed after adoptive transfer of different populations of lymphoid cells. Spleen cells deliberately immunized in vitro and in vivo against stimulator cells bearing embryo-associated antigens and which are cytostatic in vitro for targets bearing such antigens, can diminish the number of lung nodules found after i.v. transfer. In contrast, cytotoxic (in vitro) spleen cells, while capable of diminishing local (s.c.) growth of tumour cells, cannot control systemic tumour growth. Within a given solid tumour mass, the subpopulations resistant to cytostatic effector cells in vitro are the ones most likely to produce lung colonies after adoptive transfer in vivo, though they show no more local (s.c.) growth than to cytostatic-sensitive cells in vivo.

Adenocarcinoma↗
PubMed1981

Microheterogeneity in regulatory circuits for T-cell alloresponsiveness.

Mixed leucocyte cultures of responder spleen cells from individual B10 mice, challenged with irradiated allogeneic B10.D2 or B10.BR spleen cells, were used to generate discrete pools of cytotoxic T lymphocytes (CTL) with which to immunize (B10 x B10.D2)F1 or (B10 x B10.BR)F1 animals. Aliquots of the original donor B10 spleen cells were stored at -70 degrees. Eighteen days after immunization of the F1 animals, spleen and serum preparations from these mice were tested, in reciprocal fashion, for their ability to affect the development of CTL from the thawed donor B10 spleen lymphocytes in fresh cultures challenged with either the original or a third party allogeneic stimulus. Evidence for individual specific suppression by F1-T lymphocytes or by F1-serum (antibody) molecules was obtained. By priming (B10 x B10.D2)F1 mice with B10 lymphoid cells the F1 animals can also be shown to resist the otherwise lethal GvHD induced by sublethal whole body irradiation followed by intravenous challenge with B10 lymphoid cells. Using F1 mice primed and subsequently challenged with lymphocytes prepared from individual donors, self-preference in the regulation of GvHD was also seen. A similar fine specificity of regulatory cells was observed using suppressor cells from individual mice rendered neonatally tolerant of histocompatible cells (by inoculation of F1 hybrid cells within 24 hr of birth). These findings suggest that the mouse T cell alloreceptor repertoire is subject to a process of somatic diversification during normal ontogenesis. By examining the regulation of alloresponsiveness in T lymphocytes of B10.Br origin which differentiate from the appropriate stem cells in a B10 or B10.Br host, we have uncovered evidence that the T-cell alloreceptor repertoire is, in part at least, determined by the host MHC environment.

Animals↗
PubMed1980

Individual-specific (idiotypic) T-B cell interactions regulating the production of anti-2,4,6-trinitrophenyl antibody. I. Generation of suppressor T cells and antibody directed against immunocompetent cells.

It is known from several experimental systems that the production of dominant antibody idiotypes may be regulated by anti-idiotypic mechanisms. Our aim has been to test whether the potential for such control also exists in the more typical heterogeneous antibody responses of inbred mice to the trinitrophenyl (TNP) hapten, where dominant idiotypes are not recognized. CBA mice were hyperimmunized to trinitrophenylated keyhole limpet hemocyanin. Serum or lightly fixed spleen cells from these mice were injected into normal syngeneic "recipients". The serum and spleen cells from these recipients were found to have the power to suppress in vitro anti-TNP antibody responses made by further spleen cells from the donor mice. This suppression was specifically directed against the cells of the individual donor animals suggesting idiotype-related regulation.

Animals↗