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S MacRae

Publications and source records attributed to S MacRae.

At least 37 records · Page 2Linked 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↗
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

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↗
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↗
PubMed1980

Individual-specific (idiotypic) T-B cell interactions regulating the production of anti-2,4,6-trinitrophenyl antibody. II. Development of idiotype-specific helper and suppressor T cells within mice making an immune response.

The previous report demonstrated that serum and cells from CBA mice immunized with trinitrophenyl (TNP), when injected into normal, syngeneic "recipient" mice, induce the formation of apparently idiotype-specific suppressor cells and serum factors, and that such regulatory elements develop within the serum of the TNP-immunized animals themselves. In this report, it is indicated that regulator cells develop also within the spleens of TNP-keyhole limpet hemocyanin-immunized animals, and may in part be responsible for our earlier observation that T cells from TNP-immune CBA mice stimulate optimal antibody production in culture when paired with B cells from the same individual animal. While some evidence for individual-specific T helper cells was obtained, the poorer response of mismatched T and B cells could be attributed in part to Ly-2.2-bearing suppressor T cells. Overall, the results support the view that idiotype-related regulation is not confined to dominant-idiotype models but is also involved in heterogeneous anti-hapten antibody responses.

Animals↗
PubMed1980

In vitro generation from murine brow marrow cells of accessory cells with discrete antigen presentation capacity and ability to release lymphostimulatory molecules.

An investigation of the immunological accessory cell function of in vitro bone marrow derived colony forming cells has been made. Data are presented to show that such cells can present immunogenic stimuli to lymphocytes and release lymphostimulatory products that in turn replace certain macrophage functions in the immune response. The appearance of these two activities is not correlated. Considerable heterogeneity exists in terms of the ability of different populations of cells to present distinct carbohydrate antigens in immunogenic form. In addition, that different macrophage cell populations can alter the affinity of antibody produced by an optimally stimulated primed spleen cell population is reported.

Animals↗
PubMed1980

Restriction of antigen recognition in mouse B lymphocytes by genes mapping within the major histocompatibility complex.

B cells, like T cells, show genetic restrictions in their interactions with other cells. B cells from (C3H/HeJ X C57BL/6J)F1 mice were stimulated with foreign antigen (sheep erythrocytes, SRBC) in parental-strain irradiated hosts. They could be subsequently activated to antibody formation in vitro by SRBC presented on cells of the same parental type, and much less by SRBC on cells of the other parental type. The restriction was seen whether antigen was presented on macrophages or by activated T cells. Experiments with congenic mice showed that the restriction was controlled by the MHC locus. Restriction of F1 B cells to responsiveness against either parental haplotype was much more readily induced in bone marrow than in splenic populations. This restriction could be broken down by giving the irradiated host a second injection of antigen 3 weeks after the first; this probably reflects "reeducation" of the F1 B cells by SRBC associated with donor, F1-type macrophages. Normal unprimed spleen B cells also showed a strong preference for activation by SRBC in association with syngeneic activated T cells.

Animals↗
PubMed1979

Suppression of cytotoxic response to histoincompatible cells. I. Evidence for two types of T lymphocyte-derived suppressors acting at different stages in the induction of a cytotoxic response.

Spleen and thymus cell populations from normal or allograft tolerant mice have been cultured for 5 days with specific alloantigens and examined for their reactivity in three assay systems. No consistent correlation was observed between the production of cytotoxic T cells (CTL) in these cultures and the ability of such cultured cells to inhibit specifically a CML response from fresh normal spleen cells directed to the priming alloantigens. Furthermore, suppressor cells measured in this latter assay were apparently distinct from those able to inhibit the production of cytotoxic lymphocyte precursors (CTLp) from bone marrow stem cells in lethally irradiated bone marrow protected mice. Velocity sedimentation experiments confirmed that both the precursor and effector cells for the two suppressor systems were physically separable, and were distinct from CTLp or CTL, respectively. Precursor cells for the two suppressor systems investigated belong to the short-lived cortical thymus cell population.

Animals↗
PubMed1979

Suppression of cytotoxic response to histoincompatible cells. II. Analysis of the role of two independent T suppressor pools in maintenance of neonatally induced allograft tolerance in mice.

The kinetics of appearance of the precursors of SuppA cells (capable of inhibiting CTLp leads to CTL) or SuppB cells (capable of inhibiting (stem cells leads to CTLp) in neonatal mice, as well as the appearance of SuppA/SuppB cells in mice given neonatal innoculations of semiallogeneic spleen cells has been investigated. The data obtained are consistent with the idea that SuppA cells have a natural role to play in the induction of neonatal tolerance, whereas SuppB cells may be more important for the maintenance of the tolerant state. Unlike the level of SuppB cells, the level of SuppA cells in tolerant mice seems to be modulated by the presence of the tolerizing determinants. Data are provided to show that SuppB cells, once induced in tolerant mice, can adoptively transfer specific allograft unresponsiveness to newborn syngeneic mice in the absence of added tolerizing antigen, whereas SuppA cells are not able to do so. These data fit the notion that SuppB cells may be responsible for the phenotype of clonal deletion.

Animals↗