CBA/J Mouse

Abstract: PROBLEM: Recurrent spontaneous resorption in DBA/2-mated CBA/J mice has been attributed to damage by NK-lineage cells andl TNF-α beginning several days after implantation. However, some recent data have suggested CBA/J female mice have a high proportion of preimplantation embryo abnormalities resulting in detective in vitro implantation and impaired trophoblast outgrowth. Could spontaneous abortion be clue to a defective embryo («seed») rather than a hostile post-implantation uterine lining («soil»), METHOD: Mated CBA/J females were manipulated so as to have high spontaneous abortion rates and a high percent abnormal embryos, or low resorption rates and a low percent abnormal embryos. Embryos from low aborting females were transferred into high aborting female recipients that were pseudopregnant, and vice versa. RESULTS: Abnormal embryos from females with high abortion rates implanted in low aborting females and did not show any greater tendency to resorb than normally developed embryos in these recipients. By contrast, normal embryos to some extent and abnormal embryos to a much greater extent, gave a high abortion rate when the recipient female was a high aborter. CONCLUSION: Properties of the «soil» into which embryos implant determines the likelihood of success or failure (abortion). Abnormal pre-implantation embryos can be «rescued» by «good soil»; «sick soil» damages both normal and abnormal embryos. Defining the cellular and molecular mechanisms may be useful in understanding basic mechanisms leading to aborting and nonaborting pregnancy

Abstract: The antigen-specific T suppressor cell clone HF1 isolated from a CBA/J mouse made tolerant by low doses of bovine serum albumin has suppressive and cytolytic activity. The analysis of the latter gave the following results. Natural killer (NK)-sensitive YAC-1 (H-2a) and RBL-5 (H-2b) target cells are lysed whereas other NK targets, like EL4 (H-2b) or the human K562 cell line are resistant. Cytolytic activity is not antibody mediated. Its inhibition by sugar phosphate or monoclonal antibodies against LFA-1 antigens is such that HF1 can neither by typed as T killer nor as NK cells. It seems to represent a distinct T lymphocyte type.

Abstract: Immunostimulation with complete Freund adjuvant (CFA) reverses the tendency to fetal loss in the CBA/J x DBA/2J mouse. First attempts to understand the mechanisms underlying this effect were to evaluate phenotypic and functional changes in the lymphocytic cell population after immunopotentiation. We demonstrated that treatment with CFA leads to diminished responses of maternal splenocytes towards paternal alloantigens and this low response cannot be improved with exogenous interleukin-2. Lymphocytes derived from spleen, para-aortic draining lymph nodes and placenta significantly suppress maternal response to paternal antigens. The effect of low fetal resorption rate is followed by marked elevation of asialo GM-1 and HNK-1-positive cells but not followed by any change of the L3T4 or Lyt-2-positive lymphocyte population in either the spleen or in draining lymph nodes. L3T4 and Lyt-2-positive cells have not been found in the placenta. An important feature was marked elevation of Mac-1-positive cells in the placentas of CFA-treated animals. The relevance of these findings to CFA-induced fetal protection is still under investigation.

Abstract: The CBA/J inbred mouse strain constitutes an interesting in vivo model-system for studies on molecular genetics of thymus ontogeny. Using RT-PCR method we have found previously that several immune system related genes as interleukins and MHC are differentially expressed. During this period the onset of T-cell receptor beta rearrangements also occur. To know which other genes are modulated during the ontogeny of the thymus, the mRNA expression levels of fetal thymus (15 and 16 days gestation) of CBA/J mouse strain were measured by hybridization with a set of four macroarrays containing a panel of 6,144 IMAGE cDNA clones from MTB thymus library. We found 145 differentially expressed sequences; 44 were up- and 101 down-regulated in the thymus at 15-16 days gestation. Among these sequences, only 20 are identified as genes whose functions are known and 125 are still unknown. Our data demonstrated that, despite intense research on maturation of the immune system focusing on the activity of several well-characterized genes, the large scale expression profile during thymus ontogeny is still an open matter. The use of cDNA-array technology is an affordable method to identify new genes that may play a role in this phenomenon.