Murine Ig levels in scid-humo were also elevated and surface Ig-expressing cells (probably B cells) were demonstrable. Consistent with this finding we obtained evidence for the existence of human lymphocytes in scid-humo. We find markedly elevated levels of human immunoglobulins (Ig) in the serum of scid-hum0 for more than 12 weeks indicating materno-fetal transfer of human B lymphocytes. We have investigated this model further by analyzing human immune responses in the progeny of scid-huPBL (termed scid-humo). Hence, scid mice reconstituted with human peripheral blood leukocytes (scid-huPBL) provide an excellent model for analysis of the human immune response under in vivo conditions. Human peripheral blood leukocytes transplanted on CB17 scid-scid mice are transferred to their offspring Severe combined immunodeficient (scid) mice are deficient in functional T cells and B cells. Karl Thomae GmbH., Biberach and Department of Immunologyv, University of Ulm, Ulm Together, the data suggest an infectious trigger (identity uncertain) of the vasculopathy and an important genetic influence on susceptibility with heterozygosity and a SCID mouse mutation providing against abortion a degree of protection.Human leukocytes in the offspring of scid-hu/PBLĬhristoph H. Abortion rates were not reduced by treatments effective in the DBA/2-mated CBA/J mouse model but were reduced by re-establishing a new colony with defined flora (a temporary effect) and by outcrossing mice with a different (C57B1/6) background. Factors augmenting the abortion rate included the presence of embryos of the +/+ genotype in the uterus and treatment with anti-asialo GM1 antibody. Abortion was not caused by immunodeficiency leading to loss of immunotrophism because immunocompetent non-SCID CB-17 mice had a higher rate of loss. Outcrossing onto a C57B1/6 background dramatically reduced the abortion rate, indicating an important genetic effect on susceptibility with heterogeneity protecting against abortion.ĬONCLUSIONS: SCID mice on the CB-17 background do not have a high rate of successful syngeneic pregnancies, and a TNF-α induced vasculopathy may be responsible. TNF-α also appeared prematurely in pregnant scid/scid mice, but the levels were lower (and areas of necrosis smaller than in +/+ × +/+ pregnancies). Decidual tissue from mated CB-17 +/+ mice showed premature release of TNF-cc in absence of TGF-β2-related suppressor activity, and vascular lesions (fibrinoid necrosis), varying in extent, were associated with both scid/scid × scid/scid and +/+ × +/+ pregnancies. in feces and with loss of one component of the SPF flora. High abortion rates were associated both with appearance of a coagulase-negative Staphylococcus sp. Mating experiments showed a scid/+ × scid//+ cross gave the highest rate of loss, and it appeared that the presence of +/+-type embryos in the uterus could be augmenting abortion with selective discrimination against scid/scid embryos. The latter was also not affected by treatment with anti-asialo GM1 antibody or by GM-CSF and was not prevented by tetracycline (which is effective in the DBA/2-CBA/J system) or progesterone treatment. Immunocompetent CB-17 +/+ mice showed an even higher rate of loss. RESULTS: Spontaneous resorption in syngeneically mated immunodeficient SCID mice on the CB-17 background occurred at an unexpectedly high rate and could not be prevented by treatment with anti-asialo GM1 antibody or GM-CSF, both of which are effective in ameliorating abortion in DBA/2J-mated CBA/J mice. METHOD: Resorption rates were studied in a SCID CB-17 barrier facility that provided the mice used to test the role of immunology in the resorption model.
PROBLEM: Immunodeficient SCID mice on the CB-17 have been used to test the role of “rejection” in a xenogeneic blastocyst transfer model of recurrent miscarriage, but interpretation of the data requires knowing syngeneic within-species matings have a high success rate and do not require immunotrophic factors expected only in immunocompetent non-T-cell deficient mice.
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