Human Ig levels remained stable for 12 weeks and afterwards declined.These mice not only accepted autologous human PBL, but also heterologous. Furthermore, we observed that the lymphoid organs were increased in size and further differentiated compared to scid mice. We found significant levels of human Ig in the serum and detected human T and B cells in lymphoid tissue in the progeny of scid-huPBL. In the present report scid-huPBL were mated and the human and host immune status in the resulting offspring was analyzed and compared to that of parental animals. Box 1755, W-7950 Biberach, FRG Abbreviations: scid: Severe combined immunodeficient Humo: Humanized mouse scid-huPBL: scid mouse reconstituted with human PBL 0 VCH Verlagsgesellschaft mbH, D-6940 Weinheim, 1992 Ladel, Department Experimental Pathology, Dr. they may generate small numbers of Ig-producing B lymphocytes and T cell receptor-expressing lymphocytes which may cause rejection of transferred xenogeneic cells [4, 51. In this system, secondary immune responses against tetanus toxoid were shown.These as well as other data suggest that the scid mouse reconstituted with human peripheral blood leukocytes (scid huPBL) represents an appropriate model for studying human immune reactions in an in vivo setting. described the successful transfer of human peripheral blood leukocytes into these mice by demonstrating elevated levels of human immunoglobulin (Ig) levels in sera. The lack of functional T and B lymphocytes seems to directly correlate with the morphology of the lymphoid organs. The lymphoid organs of these scid are of minimal size and structurally different from those of immunocompetent mice. Because these scid mice lack functional Tand B cells they tolerate xenografts. The murine autosomal recessive mutation scid affects early lymphocyte differentiation in the inbred strain CB17 resulting in homozygous CB17 scid/scid mice (scid). Represents a major pitfall of the scid system for the study of human immune responses in vivo. This is in contrast to scid mice in which elevated Ig levels correlate with increased failure rates of reconstitution with human blood leukocytes.We propose that scid-humo provide an improved model for studying the human immune responses in an in vivo setting. Human Ig levels in scid-humo increased more rapidly as compared to normal scid mice.Thus, despite these increased B cell activities in scid-humo, transferred human leukocytes were not affected indicating that materno-fetal transfer of human cells had caused tolerization or conditioning. Not only leukocytes from autologous but also those from heterologous donors were accepted. In contrast to “leaky” scid, scid-humo accepted transfer of human blood leukocytes. In this respect scid-hum0 resembled “leaky” scid. 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 Human leukocytes in the offspring of scid-hu/PBLĬhristoph H.
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