R M Slapsys

McMaster University, Hamilton, Ontario, Canada

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Publications (11)22.46 Total impact

  • R M Slapsys · E Younglai · D A Clark
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    ABSTRACT: In both murine and human pregnancy, a novel population of small lymphocytic cells with suppressive activity accumulates in the uterine decidua. In the mouse, these suppressor cells lack T cell markers, release an interleukin-2 blocking factor, are associated with cells with cytoplasmic granules, and are deficient in the decidua of mice showing increased abortion rates with loss of resistance to attack by maternal antipaternal transplantation immunity. Small granulated cells with immunosuppressive activity do not arise as a result of decidualization alone but can be induced using trophoblast-type cells and supernatants conditioned by trophoblast-type cells. Possible mechanisms of this induction and the importance of trophoblast-decidual interaction in generating localized immunosuppressive buffer zone (chemical barrier) about the implanted conceptus are discussed.
    Regional immunology 01/1988; 1(3):182-9.
  • Renata M. Slapsys · Carl D. Richards · David A. Clark
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    ABSTRACT: The fetus resulting from allogeneic mating expresses a variety of antigens that may serve as targets for rejection by the maternal immune system. Accumulation of non-T suppressor cells into the uterine decidua of allopregnant mice may serve to prevent such rejection. It has been previously shown that the suppressor activity in decidua during the second half of murine pregnancy is predominantly associated with a population of small lymphocytes with cytoplasmic granules that lack T-cell markers and inhibit the generation of cytotoxic lymphocytes (CTL) against paternal alloantigens both in vitro and in vivo. Since natural killer cells (NK) also possess cytoplasmic granules and may regulate the murine immune response, we examined the hypothesis that the decidua-associated non-T suppressor cell may represent a regulatory type of NK cell. Similar to NK cells, the decidua-associated suppressor cell expressed FcR for IgG. Unlike NK cells, the decidua-associated suppressor cell proved resistant to treatment with anti-asialo GM1 + C'. Sedimentation velocity examination demonstrated that decidua-associated NK activity was associated with cell population with a modal sedimentation of 4 mm/hr that was larger than the decidua-associated suppressor population. Potent suppressor cell activity was also recovered from the decidua of NK deficient allopregnant bg/bg mice. Therefore, decidua-associated NK cells and suppressor cells represent two distinct populations.
    Cellular Immunology 05/1986; 99(1):140-9. DOI:10.1016/0008-8749(86)90223-6 · 1.92 Impact Factor
  • D A Clark · Slapsys RM · A Chaput · C Walker · J Brierley · S Daya · K L Rosenthal
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    ABSTRACT: The mammalian fetus expresses a variety of paternal histocompatible, oncofetal, and trophoblast antigens against which the mother can mount an immune response. Survival of the "fetal graft" appears to depend upon local immunosuppressive mechanisms in lymph nodes draining the uterus and at the intrauterine implanation site itself. Nonspecific not-T-Fc-receptor-bearing small lymphocytes containing cytoplasmic granules present in successfully allopregnant mice can suppress both the generation of maternal-antipaternal killer T cells and the infiltration of cytotoxic T lymphocytes into sponge-matrix allografts during the effector phase of the immune response. These suppressor cells are deficient at the implantation sites of xenogeneic and allogeneic mouse embryos that are susceptible to maternal immunity and are destined to resorb. A soluble suppressor factor of approximately 100,000 daltons in size can be obtained from the suppressor cells and acts to block the response of T cells to interleukin-2 by interfering with IL-2 receptors. The development of the suppressor cells in the decidua requires certain hormonal signals as well as signals provided by trophoblast cells. Freshly explanted or cultured murine trophoblast cell lines elaborate soluble factor(s) that are active in recruitment or activation of suppressor cells. Since suppressor cells may be isolated from decidua of successfully allopregnant humans, the suppressor cell mechanism and its regulation may represent a key factor in the protection of the "fetal allograft" from rejection by maternal immunity.
    American Journal Of Reproductive Immunology 04/1986; 10(3):100-4. · 3.32 Impact Factor
  • D A Clark · R M Slapsys
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    ABSTRACT: The presence or absence of a novel population of nonspecific non-T granulated lymphocytic suppressor cells in the uterine decidua correlates closely with susceptibility to maternal immunity and the outcome of the pregnancy. The fetal trophoblast appears to play a key role in the generation of this population of suppressor cells in decidua. The precise cellular and molecular events underlying suppressor cell recruitment remain unknown. The recent finding of suppressor cells in the decidua of successfully allopregnant women and the high rate of failure of human IVF embryos that is associated with a maternal mononuclear infiltration suggests that understanding the mechanism(s) by which decidual suppressor cells are regulated could have some practical applications in dealing with problems of human pregnancy failure.
    Contributions to gynecology and obstetrics 02/1985; 14:44-53.
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    ABSTRACT: The immunological survival of the antigen-bearing mammalian feto-placental unit is determined by the functional properties of the tissues at the feto-maternal interface. Antigen-specific systemic suppressor mechanisms such as suppressor T cells and nonantigen-specific suppressive serum factors appear not to play a major role in protection of the fetus. A novel type of non-MHC specific suppressor cell accumulates locally in the decidua of successfully allopregnant mice. This decidua-associated suppressor is a small lymphocytic cell possessing cytoplasmic granules, lacks T cell markers, and is deficient in number and activity at the implantation sites of viable xenogeneic Mus caroli embryos gestating in the uterus of Mus musculus animals at the time that maternal lymphoid cells begin to infiltrate the xenoembryos. These Mus caroli embryos subsequently resorb. Further experimental studies suggest that the trophoblast cells associated with successful pregnancy recruit bone-marrow derived maternal non-T suppressor cells to the decidua and thus, by an indirect mechanism, may act to protect the fetus from effector cells of the mother's immune system.
    American journal of reproductive immunology: AJRI: official journal of the American Society for the Immunology of Reproduction and the International Coordination Committee for Immunology of Reproduction 04/1984; 5(2):78-83. DOI:10.1111/j.1600-0897.1984.tb00293.x
  • David A Clark · Renata M Slapsys · B.Anne Croy · Janet Rossant
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    ABSTRACT: The mammalian fetoplacental unit bears a variety of embryonal and paternally derived histocompatibiliy antigens against which the immune system of the mother can and does react1–3. Nevertheless, there has been little evidence to suggest that these pregnancy-induced immune responses actually harm the fetus, and some investigators have suggested that immunization against paternal antigens may actually be helpful in ensuringfetal survival2–4. In this review David Clark and his colleagues briefly outline data indicating that the so-called fetal allograft' is not always as successful as we have thought, and argue that a unique type of suppressor cell which accumulates at the implantation site in the decidua early in pregnancy may play an important role in preventing maternal refection of the embryo. They also summarize current information on the role of suppressor T cells and of fetal trophoblast cells in protection of the conceptus.
    Immunology Today 04/1984; 5(4):111-115. DOI:10.1016/0167-5699(84)90045-8 · 9.49 Impact Factor
  • D A Clark · R M Slapsys · B A Croy · J Rossant
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    ABSTRACT: We recently developed a system in which fetal death consistently occurs and is associated with maternal immune reactivity against the fetus. When embryos from Mus caroli, an Asian species of mouse, are transferred to the uteri of Mus musculus, they appear normal until 9.5 days of pregnancy but are resorbed by 15 days. Death is preceded by infiltration with maternal lymphoid cells, and the dying fetuses contain Thy-1.2+, Lyt-1+2+ lymphoblasts that lyse Mus caroli target cells in a short-term 51Cr-release assay in vitro. In this paper we demonstrate that the decidual suppressor cells present during normal allogeneic intraspecies pregnancy in one uterine horn are not detectable in the decidua associated with xenogeneic Mus caroli conceptuses that have implanted in the opposite uterine horn. This evidence suggests an important role for these suppressor cells in promoting survival of the mammalian fetus.
    The Journal of Immunology 09/1983; 131(2):540-2. · 4.92 Impact Factor
  • Renata Slapsys · David A. Clark
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    ABSTRACT: : The fetus resulting from allogeneic mating in an outbred population such as man represents an antigenic graft against which the mother mounts an immune response. However, the type of immunity elicited by the “fetal allograft” does not appear to mediate graft rejection. This observation suggests that suppression of those types of immune responses that cause graft rejection may account for fetal survival. Allografts placed experimentally within the uterus appear to enjoy prolonged survival compared to grafts at other sites, and this latter finding suggests that localized suppression of graft rejection may exist within the uterus at the maternal-fetal interface. Previous studies have shown that suppressor cells which develop in the lymph nodes draining the uterus (DLN, paraaortic and renal lymph nodes draining the uterus) of allogeneically mated C3H and CBA strain mice are small lymphoid cells that sediment at 3 mm/h in unit gravity; arise early during first pregnancy, reaching maximum activity near the time of implantation (“grafting”); selectively inhibit the generation of cytotoxic T cells (cytotoxic T lymphocyte—CTL—or killer T cells) in vitro and in vivo; and are absent in the DLN of CBA mice which spontaneously resorb their litters. Furthermore, this suppressor cell population appears to be concentrated within the uterine decidua, and both DLN and decidual suppressor cells are under hormonal control. We now report that initial onset of suppression in decidua occurs more rapidly than in DLN after mating. The suppressor cell population in both DLN and decidua is resistant to destruction by anti-T serum plus complement and anti-Ly sera plus complement, and preliminary studies show that suppressor cell activity is associated with a population of granulated small lymphocytes. A soluble suppressor activity can be obtained from the decidual lymphoid population similar to that obtained in studies of the DLN suppressor cell. Small numbers of suppressor cells can prevent the infiltration of sponge matrix allografts by cytotoxic T cells in vivo. Thus, a non-T suppressor cell population may accumulate within the uterus and protect the fetal allograft from cell-mediated immune rejection.
    American journal of reproductive immunology: AJRI: official journal of the American Society for the Immunology of Reproduction and the International Coordination Committee for Immunology of Reproduction 04/1983; 3(2):65-71. DOI:10.1111/j.1600-0897.1983.tb00217.x
  • Renata M. Slapsys · David A. Clark
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    ABSTRACT: The mammalian fetus bears a wide variety of antigens against which the maternal immune system can respond. Although some of these antigens are transplantation antigens, the type of immune response mounted by the mother seems incapable of mediating graft rejection. We have previously demonstrated suppressor cells in the lymph nodes draining the uterus (DLN) that regulate the immune response in allogeneically pregnant C3H/HeJ and CBA/J mice. The suppressor cells were shown to be small lymphocytes (sedimenting at 3 mm/h at unit gravity) resistant to anti-T cell serum + complement that elaborated a soluble suppressor activity and selectively inhibited the generation of cytotoxic T lymphocytes (CTL) reactive with paternal alloantigens. Suppression could be induced in the DLN by syngeneic pregnancy or pseudopregnancy, and behaved as an anatomically localized activity during pregnancy. We now report that during first allogeneic pregnancy, the most potent suppressor cell activity is found in lymphocytes in uterine venous blood and in decidual lymphocytes. This suppressor cell population also sediments at 3 mm/h and is associated with production of a soluble suppressor factor. Substantial suppressor cell activity can also be obtained from the deciduomata of pseudopregnant mice. Local suppressor cell activity within the uterus may play an important role in ensuring the immunological success of the fetal allograft.
    Journal of Reproductive Immunology 01/1983; 4(6):355-64. DOI:10.1016/0165-0378(82)90010-9 · 2.82 Impact Factor
  • R M Slapsys · D A Clark