Allogeneic Pregnancy Research Articles

Maternal humoral immune response to incompatibility at multiple minor histocompatibility loci in mice

Mice of the H-2 b haplotype were mated with males of the same MHC haplotype, but differing at multiple minor histocompatibility loci. Mice were bled during each pregnancy and at 2-day intervals post-partum. The sera were assayed by indirect immunofluorescence for evidence of a humoral immune response to paternal minor histocompatibility antigens. Alloantibody was first detected in the post-partum period following the third pregnancy, and was also detected during the fourth pregnancy. Thereafter, alloantibody levels dropped and by the post-partum period following the fifth pregnancy, fell to control values. Assays on a panel of cells from mice of different inbred strains revealed specificity of the alloantibody to H-3.1, H-4.1 and H-7.1 antigens. A conventional dye exclusion cytotoxicity test revealed the pregnancy-induced alloantibody did not exhibit complement-dependent cytotoxicity. These findings are discussed in relation to the regulation and functional significance of the humoral immune response in allogeneic pregnancy.

The role of RT1 antigen differences in semi-allogeneic rat pregnancy.

The immunological mechanisms involved in sustaining normal semi-allogeneic pregnancies and in the enhancement of organ allografts were investigated in inbred rats. The antigenic targets for alloantibodies formed after leucocyte transfusions and multiple allogeneic pregnancies were defined by the EA rosette inhibition (EAI) assay in several congenic and recombinant inbred rat strains. Alloantibodies produced by leucocyte immunization (conventionally induced antisera) were directed only to RT1-encoded (major histocompatibility complex, MHC) antigens. Both RT1A (class I MHC) and either RT1B, D (class II MHC) or RT1C (Qa-like) antigens were targets for these alloantibodies; responses to the latter three antigens could not be separated with available congenic recombinant inbred rat strains. Alloantibodies produced as a consequence of multiple semi-allogeneic pregnancies (pregnancy-induced antisera) were directed only to RT1A antigens. Allogeneic pregnancies in which the paternal strain differed from the maternal strain only at the RT1A gene locus produced suppression of a subsequent maternal immune response.

Humoral immune responses in murine pregnancy. V. Relationship to the differential immunogenicity of placental and fetal tissues

The nature of the humoral immune response induced in virgin female mice by injections of F1 placental and fetal tissues has been examined and compared to that induced by immunization with F1 adult spleen cells and by multiple allogeneic pregnancy. In a ‘responder’ strain mouse, as defined by the ability of multiple allogeneic pregnancy to elicit an anti-paternal humoral immune response, both F1 placental and fetal tissues induced the formation of alloantibodies primarily of the IgG1 sub-class, similar to those induced by allogeneic pregnancy, but different from those elicited by adult spleen cells. However, only the placental tissues induced alloantibodies possessing all the characteristics of those appearing in multiparous allogeneic pregnancy. In contrast, the alloantibodies induced by the injected fetal tissue possessed complement-dependent cytotoxic activity, indicating that the inability of pregnancy-induced alloantibodies to mediate cytotoxicity may not be related to their restriction to the IgG1 sub-class. In a ‘non-responder’ mouse strain, where multiple allogeneic pregnancy does not lead to a maternal alloantibody response, F1 placental tissues, in contrast to fetal and adult tissues, failed to induce a humoral immune response. Injection of F1 placental tissue therefore elicits responses that mimic both the properties and the strain-dependent distribution of the alloantibodies identified in normal murine pregnancy. This implies that the immunogenic stimulus in pregnancy emanates from the placental rather than the fetal compartment of the allogeneic conceptus.

The effect of cyclosporine on humoral and cellular alloreactivity to allogeneic pregnancy in rats.

We have evaluated the effect of a therapeutic dose (10 mg/kg/day) of the immunosuppressant cyclosporine (CsA) on humoral and cell-mediated immunity in rats during an allogeneic first pregnancy. Virgin female Lewis rats mated with DA males and treated with CsA vehicle produced a humoral response, as measured by both the erythrocyte rosette inhibition (EAI) and indirect hemagglutination assays. The capacity of Lewis splenocytes to mediate a graft-versus-host (GVH) reaction in six-week old F1 (Lewis X DA) hybrid rats was unaffected by either pregnancy or CsA. In mothers treated with CsA, however, no antibody production was detected, and a significant reduction in GVH reactivity was observed using their cells. This reduction was specific for the paternal strain. When compared with vehicle-treated primiparas, suppression of the immune response by CsA had no effect on either the number or viability of fetuses present in utero at day 20. These data suggest that antipaternal antibodies may not be essential to protect the fetus when there is concomitant suppression of the capacity of the mother's T cells to express a cell-mediated antipaternal response.

Collagen-induced arthritis and pregnancy in mice: the effects of pregnancy on collagen-induced arthritis and the high incidence of infertility in arthritic female mice.

Collagen-induced arthritis (CIA) in mice is a model of inflammatory polyarthritis that has many features similar to human rheumatoid arthritis. In rheumatoid arthritis, pregnancy leads to amelioration of the disease while exacerbation develops after delivery. We used the CIA model to elucidate the role of pregnancy on disease and vice versa. The onset of arthritis in pregnant mice was delayed in the B10.RIII strains immunized with native porcine type II collagen 7-12 days prior to syngeneic [B10.RIII (susceptible to CIA) X B10.RIII] and allogeneic (B10.RIII female X B10.K male that are CIA resistant) pregnancy. In contrast, when mice were immunized on days 1-6 of pregnancy, the onset of arthritis was earlier as compared with controls. In addition, once the mice developed CIA after delivery, the disease showed markedly rapid progression as compared to the control immunized group. Humoral immune responses to type II collagen showed significantly decreased levels on day 14 (at late stage of pregnancy) both in syngeneic and allogeneic postmating immunized pregnant mice. The same effect was also seen in allogeneic premating immunized pregnant mice on day 21 (at mid-stage of pregnancy). The levels of these antibodies increased after delivery. Subclasses of IgG1 and IgG2a antibodies to type II collagen were suppressed during pregnancy. In the pseudopregnant group, these antibodies showed decreased levels on day 14, but did not differ from the control groups on day 21 and 28. Some immunoregulatory changes may play a role in these alterations in pregnant arthritic mice. In comparison to the effects of syngeneic (susceptible X susceptible) pregnancy on CIA, allogeneic (susceptible female X resistant male) pregnancy seemed to be beneficial for the affected individuals. Litter size and mean birth weight were not affected by immunization of type II collagen. After onset of CIA, both syngeneic and allogeneic matings failed to produce offspring in arthritic female mice. The estrus cyclicity was highly disturbed in arthritic female mice and gonadotropin stimulation in arthritic mice induced significantly less ova in oviducts and maturing follicles as compared to nonarthritic controls. Immunological factors yet to be elucidated may be involved in this ovarian dysfunction.

Thymus-dependent increase in splenic T cell population in postpartum mice.

Cell dynamics in the thymus and spleen of mice during the first allogeneic pregnancy and during postpartum were investigated. A considerable decrease in the number of thymocytes occurred at midpregnancy and was sustained until postpartum. There was an increase in the number of splenic T cells on the third postpartum day. These splenic T cells were shown to have the Lyt-1+ 2-phenotype, as determined by multiparameter analysis, and their responsiveness to Con A was increased compared with splenic T cells of virgin mice. Since such T cells were not observed in the postpartum spleen of adult thymectomized mice, they may have derived from the thymus. The response to Con A by normal virgin spleen cells was depressed when spleen cells from 3-day postpartum mice were added to the culture as the third party cells. Thus, the increased number of splenic T cells may act as inducer cells in the suppressor circuit during postpartum.

Sex-dependent local cellular immunity to alloantigens.

A local component of cellular immunity was detected in mice that had been immunized against histocompatibility antigens. The status of this local immunity was determined using a node-onto-kidney (NOK) assay in which lymph nodes draining the site of immunization as well as distant (nondraining) lymph nodes of the immunized mice were grafted onto the kidneys of mice of the immunizing strain. In this assay, the weight gained by each node piece was taken as a measure of its immunological responsiveness. The responsiveness of a draining lymph node was directly compared with that of a distant node after both had been grafted onto the same host kidney. We consistently found that the draining lymph nodes of immunized male mice were more responsive than their distant nodes, whereas the draining lymph nodes of immunized female mice were less responsive than their distant nodes. Male mice were converted to the female pattern of hyporesponsiveness in the draining nodes by performing bilateral orchidectomy, suggesting that the male pattern depends upon the presence of testicular hormones. Additional studies showed there was a significant reduction in the reactivity of uterine draining lymph nodes during both syngeneic and allogeneic pregnancy, raising the possibility that the female pattern of hyporesponsiveness facilitates fetal survival by reducing the maternal immune response to fetal antigens and alloantigens during pregnancy.

Active anti-paternal immunization does not affect the success of marsupial pregnancy

Active anti-paternal immunization does not compromise pregnancy in eutherian mammals. However, in an earlier study in a marsupial, grafting with paternal skin appeared to have resulted in transient infertility. In the present study, by critically monitoring the breeding efficiency of tammar wallabies sensitized against their mate's transplantation antigens, we aimed to resolve the question of immunologically mediated infertility in marsupials. Eight experimental females received two full-thickness skin grafts from their prospective mate and eight controls grafts of their own skin. The experimental group were monitored for 30 reproductive cycles and produced 24 pouch young (PY), whereas the control animals produced 28 young from 33 cycles. Five of the 11 apparently non-fertile cycles were judged to be normal pregnancies where the young had failed to reach the pouch (cycle length < 28 days: rapid plasma progesterone decline coincident with oestrus). True infertility was thus limited and, although occurring mainly in the male-skin grafted group (5 cycles), this was not significantly different (χ 2, P > 0.5) from the controls (1 cycle) and represented the effect of one very poor breeder. We conclude that allogeneic pregnancy in marsupials is not compromised by active anti-paternal immunization. Infertility observed here, and in the earlier study, reflected disturbance of breeding owing to handling of the animals or the poor reproductive efficiency of individual animals in small experimental groups.

Characterization of hematogenous cellular constituents of the murine decidua: a surface marker study

Decidual tissue, which includes typical (stromal type) decidual cells as well as infiltrating leukocytes, appears to play a local immunoregulatory role in the maintenance of pregnancy in nature. The present study evaluated the contribution of numerous leukocyte subsets characterized on the basis of morphology combined with cell surface markers to the development of murine decidua during syngeneic ( CBA ♀ × CBA ♂ ) and allogeneic ( CBA ♀ × C57BL/6 ♂ ) pregnancy. Collagenase dispersed decidua were subjected to total and differential counts and cell surface labeling for a radioautographic identification of various markers: S-IgM on B cells, Thy-1 on T cells, neither marker on null lymphocytes, Lyt- (1 or 2 or 1,2) antigens on T cell subsets, Mac-1 and I-A on macrophages, using 125I-labeled monoclonal antibodies or a sandwich labeling with 125I-protein A. The total cellularity of decidua basalis showed a biphasic rise in both pregnancies, with peaks on day 11 and days 15 and 16, but the allopregnant decidua showed a higher accumulation of all cell types indicating that an allogeneic conceptus causes an augmented deciduogenesis. The number of decidual cells, the most frequent cell class, rose to a peak on day 11 followed by a decline possibly due to cell death. The number of lymphocytes, the next frequent cell class, showed a parallel pattern initially, followed by a sharp secondary rise on day 16. This rise may be due to a withdrawal of progesterone, an antiinflammatory hormone. Null cells predominated amongst decidual lymphocytes (45–80%), as well as in the progestational endometrium (53%), indicating a hormonal control of their accumulation. The frequency of B cells was low (10–13%) and T cells (25–45%) comparable to that in the blood, with Lyt-1 only class being the most common T cell subset. Allopregnant decidua also showed a late rise in the total number of Lyt-2 only cells which may have a suppressor function. Macrophages, the next common leukocyte class, all expressed Mac-1. Their number rose to a plateau by day 12, but at a higher level in allopregnancy. I-A (needed for antigen presentation) was expressed by an increasing proportion (5–60%) of macrophages with advancing gestation. These findings provide a basis for further functional studies.

Lack of a requirement for a maternal humoral immune response to establish or maintain successful allogeneic pregnancy.

In general, breeding pairs are not major histocompatibility complex (MHC)-compatible, and therefore the fetoplacental unit can be considered as a natural allograft. In many mammals pregnancy leads to the production of nonlytic antibodies of antipaternal MHC specificity. It has been suggested that these protect the semiallogeneic fetus from rejection by acting as blocking or enhancing factors--or, alternatively, that they are part of a humoral response involved in the establishment of normal pregnancy. These hypotheses were tested in allomated mice made B cell deficient by continuous treatment with alpha IgM mu antiserum. The status of the maternal immune system was assessed by in vivo antibody production, in vitro mitogen responses, and allograft rejection. By these criteria B cell function could not be demonstrated in alpha IgM mu treated female mice, but T cell responses were unaffected. Allogeneic pregnancy, however, was not compromised by this humoral immune system dysfunction--litter size and neonatal survival being the same in the alpha IgM mu and control serum-treated groups. These results indicate that a maternal humoral immune response is not essential for the establishment of pregnancy or the survival of the semiallogeneic fetus.

Stimulation of alloreactive cytotoxic T cells by paternal major histocompatibility antigens during murine pregnancy.

In an effort to elucidate T cell reactivity toward paternal major histocompatibility (MHC) antigens during pregnancy, the ability of pregnant mice to develop alloreactive cytotoxic T lymphocytes (CTL) was studied in individual multiparous females mated with MHC congeneic strains of B10 background. Spleen cells obtained from B10.BR females mated to allogeneic males manifested strikingly higher CTL than those from animals mated to syngeneic males or from virgins; syngeneically mated animals were equivalent to virgin controls in CTL responses. The augmented CTL response in allogeneic pregnancy was detected not only by stimulation with the paternal MHC antigens but also by an unrelated MHC haplotype. However, this augmentation was found only during pregnancy in that 2-5 days after the delivery the CTL activity in allopregnant animals returned to a level comparable to that of virgin controls. No suppressor cells were detected at this stage. These observations suggest that maternal T cells recognize MHC disparity with the fetus in some way during pregnancy. Anti-MHC antibodies, immunoglobulin (Ig) M, and IgGs of all subclasses were not detected in these animals throughout multiple pregnancies.

Active suppression of host-vs-graft reaction in pregnant mice. VI. Soluble suppressor activity obtained from decidua of allopregnant mice blocks the response to IL 2.

The mammalian fetus expresses a variety of antigens against which the maternal immune system can react and which in an allogeneic mating bears paternal transplantation antigens. Although these antigens may be expressed on the fetal trophoblast cells that contact maternal uterine decidua, the "fetal allograft" is not usually rejected. Previous studies have demonstrated the presence of nonspecific non-thymus-derived suppressor cells in the lymph nodes draining the uterus and in decidua of laboratory mice undergoing first allogeneic pregnancy. These suppressor cells appeared to be small lymphocyte cells that inhibit the generation of cytotoxic T lymphocytes (CTL) in vitro and in vivo and elaborate a nonspecific non-MHC-restricted soluble suppressor activity when cultured for 48 hours at 37 degrees C in vitro. We now report that soluble suppressor activity obtained from the decidua (DS) of allopregnant C3H/HeJ mice inhibits both the primary and secondary (memory) CTL response in vitro but does not inhibit lysis of target cells by preformed CTL. DS did not suppress the proliferation of YAC lymphoma cells, P-815 cells, or a C3H placental trophoblastoma line. Suppressor activity was obtained from anti-thy-1.2 + complement-resistant cells in the decidua, could also be obtained from the decidua of allopregnant CD1 nu/nu mice, and was associated with a single peak of activity of approximately 100,000 daltons on Sephacryl 200 chromatography. Suppression could not be overcome by adding either crude or HPLC-purified IL 2 to the mixed lymphocyte cultures in vitro, and both crude and column-purified suppressor factor inhibited the IL 2-dependent proliferation of H-Y cells (a cloned T cell line with NK activity). Furthermore, DS inhibited the IL 2-dependent generation of cytotoxic effector cells in vitro in the absence of allogeneic stimulator cells. Thus, a soluble suppressor factor obtained from non-T cells present in the decidua of successfully allopregnant mice could block the response to IL 2 and inhibit the generation of both specific and nonspecific cytotoxic effector cells. The significance of this inhibition with respect to survival of the "fetal allograft" is discussed.

Allogeneic pregnancy in B-lymphocyte deprived CBA/Ca mice — Effects on maternal lymphoid organs and fetal survival

A number of female CBA/Ca (H2-k) mice were injected with rabbit-anti mouse IgM every 2 days throughout their life cycle in order to prevent their development of immunocompetent B-lymphocytes. The efficiency of the anti IgM-treatment was good in the group of mice used, and all experimental mice almost completely lacked 1) surface Ig-staining cells (immunoperoxidase ABC method), 2) serum IgG (ELISA technique), and 3) Ig-secreting cells (protein A plaque assay). All experimental mice contained a functioning T-cell pool, as recorded in vitro by conA-stimulation and one-way MLC. At an age of 40–60 days these mice were allowed to mate allogeneically with C57/B1 (H-2b) males. No harmful effects of the anti-IgM treatment on the first pregnancy cycle were found, and B-cell-deprived mice delivered as many healthy litters as did the controls. It was also observed that the enlargement of the spleen and uterus-draining nodes was of the same magnitude in both experimental and control mice at the end of the first pregnancy.

Immunoglobulin-secreting cells in various maternal lymphoid tissues during syngeneic and allogeneic murine pregnancy

The effects of syngeneic (CBA×CBA) and allogeneic ( CBA× C57 B1 ) pregnancy on immunoglobulin (Ig)-secreting cells in various maternal organs/tissues have been investigated by using the protein A plaque assay. The following organs/tissues were examined: a ) spleen, b ) cervical nodes, c ) inguinal nodes, d ) mesenteric nodes, e ) paraaortic (uterus-draining) nodes, f ) Peyer's patches, and g ) bone marrow (femur). The changes observed were similar and of the same magnitude in all pregnant animals, irrespective of the type of mating. At mid-gestation (day 14) a distinct increase in Ig secretors was observed, predominantly in the spleen. At the end of pregnancy (day 20) the para-aortic nodes contained dramatically increased numbers of plaque forming cells. A slight increase in both IgM and IgG-secreting cells was also seen in bone marrow at the very end of pregnancy, while Peyer's patches and the nodes of neck and legs appeared to be unaffected throughout the period of gestation.

Existence of suppressor cells in the spleen of allogeneic and syngeneic primiparous pregnant mice

Mixed lymphocyte reaction (MLR) and in vitro induction of cytolytic cells against alloantigens were investigated using spleen cells from primiparous mice mated allogeneically or syngeneically. One-way MLR was reduced significantly in degree not only in allogeneic but also in syngeneic pregnant mice. MLR of virgin spleen cells was suppressed when mitomycin C-treated spleen cells taken from syngeneic or allogeneic pregnant mice were added as regulator cells. These suppressive effects disappeared when regulator cells were treated with anti-Thy 1 or anti-Lyt 2 serum plus complement. Generation of cytotoxic lymphocytes from syngeneic or allogeneic pregnancy spleen cells in MLR was depressed compared with that from virgin spleen cells. The addition of pregnancy spleen cells to MLR suppressed in vitro generation of cytotoxic lymphocytes from virgin spleen cells. These results indicated that reduction of in vitro cellular responses of pregnancy spleen cells was due to suppressor cells in the spleens. These cells suppressed non-specifically the reactions to alloantigens and could be detected both in allogeneic and syngeneic primiparous pregnancies.

An evaluation of the maternal natural killer cell population during the course of murine pregnancy

Earlier work from this laboratory revealed an increase in the level of null (Thy-1 −, IgM −) lymphocytes in the maternal lymphoid organs during the first pregnancy in the mouse that was more pronounced during allogeneic pregnancy than during syngeneic pregnancy. In view of the suggestive evidence for the bone marrow origin of these null cells, the functional significance of the null cell rise was explored in this study by an examination of (1) splenic NK activity as measured by the 51Cr-release assay using YAC-1 lymphoma targets, (2) the incidence of NK lineage cells in the spleen as measured by the ability of splenic null lymphocytes to bind YAC-1 lymphoma targets, and (3) the possible presence of a NK target structure on placental trophoblast cells, studied with a cold target competition assay. Results revealed that the absolute levels of null lymphocytes, NK lineage cells, and NK activity in the spleen increased moderately and nearly at the same time during syngeneic pregnancy. During allogeneic pregnancy all three parameters increased more significantly, the rise in the levels of NK activity and NK lineage cells somewhat preceding the null cell rise, suggesting preferential recruitment of active NK cells within the null lymphocyte population of the spleen. Trophoblast cells appeared to share NK target structures with YAC-1 lymphoma cells, suggesting that a rise in the NK cell level in both pregnancy types may represent a response of the mother to such target structures. Since the density of such moieties was similar for homozygous and heterozygous trophoblasts, a higher NK cell response during allogeneic pregnancy is considered to result indirectly from an alloreactive response of the mother to the paternally encoded antigens on the fetoplacental unit, possibly from a stimulation of interferon producing cells such as macrophages. Nevertheless, such a response appears to be harmless for the allogeneic conceptus.

Fate of antipaternal H-2 antibodies bound to the placenta in vivo.

We have previously demonstrated that the placental spongiotrophoblast and yolk sac venous plexus express paternally derived H-2K and D (class I) antigens in a manner accessible to maternal circulation, and that the placenta serves to prevent antipaternal antibodies from reaching the fetus. Kinetic studies indicated that the placenta is capable of reexpressing its H-2 antigens after having been bound by anti-H-2 antibodies, suggesting that the placental cells somehow have the ability to eliminate the bound antibodies. In order to investigate the fate of the antibodies, we have followed the uptake and fate of radiolabeled anti-H-2Kk monoclonal antibody in the placentas of target allogeneic and control syngeneic pregnancies. Chromatographic analyses indicate that most of the intercellular radiolabel is associated with fragments smaller than IgG, and similar degradation was not observed with syngeneic control placentas. We conclude that the placenta is capable of binding, ingesting, and then digesting antipaternal H-2 antibodies, further substantiating the immunoabsorbent barrier hypothesis of allogeneic fetal survival.

In vitro activity and in vivo correlates of alloantigen-specific murine suppressor T cells induced by allogeneic pregnancy.

The fetus that results from allogeneic mating in an outbred population bears a variety of antigens against which the maternal immune system reacts, but the type of immunity that is elicited by pregnancy does not mediate graft rejection. Previous studies have demonstrated the presence of nonspecific non-thymus derived suppressor cells in the lymph nodes draining the uterus (DLN) and in the uterine decidua during first allogeneic pregnancy. These suppressor cells appear to be small lymphoid cells that inhibit the generation of cytotoxic T cells (CTL) against paternal alloantigens. We now report that after a single allogeneic pregnancy, C3H and A strain mice develop paternal alloantigen-specific suppressor T cells (Thy-1.2+, Lyt-1-2+) that are distributed systemically in peripheral lymph nodes and spleen. These suppressor cells appear to act directly on CTL generation because the frequency of CTL precursors and the ability to produce T helper cells in response to paternal alloantigens remains unchanged after allogeneic pregnancy. Suppressor T cell activity could be detected both in vitro and in vivo, and the presence of suppression in vivo was associated with increased uterine weight 5 days after inoculation of allogeneic paternal tumor cells into the uterus of pseudopregnant mice. Nevertheless, both subcutaneous and intrauterine tumor inocula regressed in these mice with suppressor T cells. The possible role of suppressor T cells in contrast to non-T suppressor cells in successful reproduction and allopregnancy-induced tolerance is discussed.

Impairment of the thymus-dependent humoral immune response by syngeneic or allogeneic pregnancy

Pregnancy results in a diminished capacity of the gravid mouse to respond to thymus-dependent antigens. The IgM response to thymus dependent and independent antigens is relatively unaltered whereas the IgG response to thymus-dependent antigens is markedly suppressed in both syngeneic and allogeneic pregnancy. The impairment of the humoral immune response is not due to loss of antibody-forming precursor lymphocytes (AFPL) from the spleen since their number remains unaltered. During pregnancy the spleen becomes enlarged and the precursor frequency is diluted somewhat but the AFPLs retain their normal activity in vitro. This implies an alteration in their amplification by accessory cells (T cells or macrophages) is responsible for the impaired IgG responses.

Active suppression of host-vs-graft reaction in pregnant mice. IV. Local suppressor cells in decidua and uterine blood

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.