The Effect of Pregnancy on Lymph Node Weight in the Mouse (original) (raw)
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Journal of Leukocyte Biology, 2005
In the present study, we evaluated whether lymphocyte cytokine production during human and rat pregnancy shifts toward T helper cell type 2 (Th2) cytokine production. Therefore, blood samples were taken during the follicular and luteal phase and during pregnancy in rats and humans. Whole blood was ex vivo-stimulated with phorbol 12-myristate 13-acetate and calcium ionophore and intracellular interferon-␥ (IFN-␥) and interleukin (IL)-4 production, and the percentage of cells in the various lymphocyte populations was measured using flow cytometry. Rats and humans adapted their immune responses to pregnancy but have different strategies: During human pregnancy, the percentage of lymphocytes producing IFN-␥ was decreased, and the percentage IL-4producing lymphocytes was not affected. The rat adapts its immune response to pregnancy by decreasing the total number of the various lymphocyte populations, and the percentage of IFN-␥-or IL-4-producing lymphocytes was not affected or increased (% IFN-␥-producing cytotoxic lymphocytes). It is speculated that during rat pregnancy, there is no need to decrease the number of IFN-␥producing lymphocytes, as in nonpregnant rats, the total number of IFN-␥-producing lymphocytes after stimulation is relatively low, and there is no necessity for a further decrease. In nonpregnant humans, the percentage IFN-␥-producing lymphocytes is much higher and probably dangerous for pregnancy, and therefore, this percentage needs to decrease during pregnancy. In conclusion, although the data from humans concur with the Th1/ Th2 paradigm, the data from rats do not concur with this paradigm. The present studies therefore challenge the classical Th1/Th2 paradigm during pregnancy.
Impact of mouse pregnancy on thymic T lymphocyte subsets
Reproduction, Fertility and Development, 2012
It has been reported that fetal lymphoid progenitor cells are acquired during gestation and are able to develop in the maternal mouse thymus into functional T cells. Moreover, previous pregnancies increase the number of fetal cells in the mother. In the present study, we investigated whether mouse pregnancy induces changes in T lymphocyte subsets in the maternal thymus. We determined the T lymphocyte subsets in two allogeneic cross-breedings, namely CBA/J × BALB/c (normal) and CBA/J × DBA/2 (abortion prone), and investigated the effects of the age and parity of the female, as well as pregnancy outcome, on thymocyte populations. In addition, hormonal effects were evaluated in a syngeneic combination (CBA/J × CBA/J). We found that during pregnancy both hormonal and allogeneic stimuli induced a reduction in the CD4+CD8+ subset with an increase in the CD4+CD8– population. Only young females of the normal combination exhibited an increase in the CD4–CD8+ population. All young mice showed...
Lymphokine production by decidual cells in allogeneic and syngeneic murine pregnancy
Cytokine, 1993
The importance of T cells during pregnancy has been well established in the murine system. Depletion of CD4 and/or CDS positive cells from the maternal circulation increases fetal abortion and inhibits placental and fetal growth. T cell mediated regulation depends on T cell-derived lymphokines such as IL-6, IL-lo, GM-CSF and IL-3. Among these factors, GM-CSF and IL-3 have been shown not only to stimulate trophoblast growth but also to promote placental function. All these growth factors having a short half life in vivo must exert their effect proximally to the site of production. In the present study, biologically active GM-CSF and IL-3 produced by T cells in the maternal decidual cap, which is the closest to the fetoplacental unit maternal component, was detected. Cytoplasmic staining of total decidual cap cells in various strain combinations, using monoclonal antibodies to lymphokines, showed that the numbers of cells producing these factors vary depending on the day of pregnancy and on the strain combination used. Using indicator cell lines and neutralizing antibodies, it was seen that GM-CSF and IL-3 are produced at the eleventh day of pregnancy and secreted in both allogeneic and syngeneic pregnancies by decidual cap cells. T cell depletion experiments in vivo showed that these factors are produced by T lymphocytes. The production and secretion of biologically active CSF-1 was also evaluated in this study. Although this is not a T cell-derived lymphokine, it is shown to be produced in the uterus and affect trophoblast growth. The results indicate that on the eleventh day of pregnancy only syngeneically pregnant mice produce sufficient quantities of CSF-1 to stimulate biologic activity. It is therefore demonstrated that the maternal immune system stimulates the growth of the fete-placental unit, obeying different rules in allogeneic and syngeneic pregnancy.
Journal of Anatomy, 2004
Mouse and vole embryos were allogeneically and xenogeneically transferred into pseudopregnant CD-1 and immunodeficient ( scid ) female mice, and we investigated the distribution of immunocompetent cells, uterine natural killer (uNK) cells, mast cells and macrophages, in the implantation sites on days 6, 7 and 8 of gestation. The survival rate of the vole embryos decreased gradually with increased gestation, but the rate was higher in the scid uteri than in the CD-1 mice. The number of uNK cells increased markedly at the mesometrial triangle and the outer decidual area in the CD-1 uteri containing vole embryos; by contrast, scid uteri having vole embryos showed almost the same number as those having mouse embryos. Mast cells were present in large numbers at the myometrium, but rarely in the decidua in all types of pregnant uteri. Cells at the myometrium were more numerous in xenogeneic than in allogeneic transfer. Many mast cells appeared in the inner decidua where xenogeneically transferred vole embryos were dead and aborted. Macrophages were present in the outer decidua and myometria in all types of pregnant uteri, and their distribution pattern did not change even in aborted uterine sites. These results suggest:
Natural lymphocyte activation in postnatal development of germ-free and conventional mice
Annales de l'Institut Pasteur / Immunologie, 1988
The degree of activation of B and T cells in the developing spleen during postnatal life was studied in germ-free (GF) and specific-pathogen-free (SPF) BALB/c mice of the same breeding stock. We found that the progeny of GF raothers up to 3 weeks of age contain higher numbers of activated splenic ceils than baby SPF mice, thus suggesting qualitative differences in maternallyderived antibodies. This ~ advantage >> of GF mice is also indicated by an anticipated maturation of the splenic lymphoid compartment and is reflected in higher frequencies of B and T lymphocytes in adult life. In both kinds of mice, the frequency of activated cells is very high at birth and then declines, reaching minimal values by 4 weeks of age. Later, activated B ceils increase sharply in SPF mice, suggesting polyclonal activation mediated by bacterial products. Results are discussed on the basis of the mutual influences between B and T cells in the establishment of a functional network.
Fetal and Postnatal Development of T-lymphocyte Subpopulations
Acta Veterinaria Brno, 2002
Changes in individual subpopulations of lymphocytes (mainly CD2 + , CD4 + and CD8 +) in primary and secondary lymphatic organs and circulating blood were observed in pig fetuses between days 51 and 112 of gestation, and in circulating blood in postnatal piglets. The technique of flow cytofluorimetry was used and binding of specific monoclonal antibodies was visualised using polyclonal antibodies against mouse or rat Ig marked with fluorochroms (PE and FITC). As soon as on day 51 of gestation, CD4 + and CD8 + T lymphocytes were demonstrated in porcine thymus. Their relative and actual numbers continued to increase markedly. When this increase was expressed in terms of age with subsequent intrapolation, the changes in CD4 + /CD8 + phenotype expression could be expected around day 40, i.e. in the period, when thymus cortex and medulla are not yet morphologically differentiated. In the spleen only CD2 + cells were found on day 51 of gestation. Expression of lymphocytes with CD4 + and CD8 + receptors was shown on day 60. Their relative and actual numbers increased with age. This increase when expressed per whole organ made a difference of three orders of magnitude. In lymph nodes, only changes from day 90 were followed. In this secondary lymphatic organ, the percentage of T lymphocytes with CD4 + and CD8 + markers was higher than that in the spleen. The CD4 + /CD8 + ratio in spleen and thymus gradually decreased with advancing age to 1 with a slightly dominant CD4 + lymphocyte subpopulation. On the other hand, in lymph nodes of pig fetuses CD8 + lymphocytes prevailed (index 0.85). In the postnatal period, a marked increase of cytotoxic CD8 + lymphocytes occurred in peripheral blood of 28-day-old piglets. Thus the CD4 + /CD8 + index decreased from 1 to 0.2. This characteristic of lymphocyte subpopulations in circulating blood is also typical of adult individuals. The numbers of B lymphocytes with IgM receptors in circulating blood increased gradually from day 90 of prenatal development until day 28 h of postnatal life both in relative and actual terms.
Effect of Pregnancy on Thymic T Cell Development
American Journal of Reproductive Immunology, 1996
The thymus gland decreases in size during pregnancy. The significance of this alteration is not known. METHOD: In this report, we examined thymic function by evaluating the development of T lymphocytes in the thymus of pregnant Balb/c mice at 15 and 20 days gestation using multi-color flow cytometry. Comparative analysis was made with non-pregnant mice, postpartum lactating mice, and postpartum non-lactating mice. RESULTS: Progressive reduction of thymic size and cellularity during pregnancy was observed. All of the CD4 and CD8 defined subsets were reduced, with a disproportionate loss of CD4+, CD8+ double positive cells. Examination of the CD4-, CD8-double negative compartment revealed a predominance of TCR a$+ double negative cells, and a striking loss of precursor cells. The CD3-, CD4-, CD8-triple negative thymic subset was composed almost entirely of the earliest population (CD44+, CD25-), with the remaining maturational stages (CD44+, CD25+; CD44-, CD25+; and CD44-, CD25-) depleted. At 2 weeks postpartum, the subset ratios normalized, and the total cell count showed recovery. CONCLUSION: T cell development is blocked at the precursor level during the mouse pregnancy. These effects are transient, and gradual recovery is observed in the postpartum period.
Journal of immunology (Baltimore, Md. : 1950), 1979
The responses of lymphoid cells from the thymus, lymph nodes, and spleen of male and female BALB/c mice were evaluated to determine if sex-related variations in immune expression could be found. Immunologic assays used included blastogenic responses to mitogens, mixed lymphocyte responses, and direct and indirect measurement of plaque-forming cells against soluble and particulate antigens. The results indicated that responses of spleen cells from young adult female mice were higher than those of males in all comparative tests. Little or no differences between the sexes were observed in the mitogenesis of lymph nodes and thymuses. Newborn mice did not demonstrate the sex-associated immune differences. Among the weanling mice slight differences between male and female spleen cells responsiveness to mitogenic agents were observed.
Transplantation and growth characteristics of human fetal lymph node in immunodeficient mice
Experimental Hematology, 2000
Objective. The lymph node is an integral component of the immune system and the major site of antigen-dependent lymphocyte proliferation and differentiation. Development of animal models possessing functional primary human lymph nodes will have a significant impact on research in lymphopoiesis and immune response. To date, successful transplantation of primary human lymph nodes in rodents has not yet been reported. This work was undertaken to develop a reliable methodology to engraft primary human fetal lymph nodes in immunodeficient mice. Materials and Methods. Three different sets of parameters, including three different transplantation sites in the mice, two different strains of immunodeficient mice, and two different preconditioning regimens, were evaluated. The growth characteristics of the implanted primary human fetal lymph nodes were examined 3 months after transplantation by histologic, immunocytochemical, and flow cytometric methods. Results. Transplantation of primary human fetal lymph nodes into subcutaneous pouches in the ears in severe combined immunodeficiency (SCID) mice preconditioned with etoposide reproducibly give rise to Ͼ 80% engraftment. The engrafted primary human fetal lymph nodes undergo massive growth ( Ͼ 200-fold) and retain the same histology and cellular composition as fresh human fetal lymph nodes from the same donors. Conclusions. We report, for the first time, the development of a reliable methodology to successfully engraft human fetal lymph node in SCID mice. The engrafted human lymph nodes are visible and accessible to experimental manipulations. This SCID-hu mouse model with human lymph node should provide a physiologically relevant system to investigate lymphopoiesis, immunologic response, and virus-mediated immunosuppression.