Long term substitution and specific immune responses after transfer of bovine peripheral blood lymphocytes into severe combined immunodeficient mice

The long term immune responsiveness of bovine peripheral blood lymphocytes engrafted into seven combined immunodeficent mice (bovine PBL SCID mice) wa s analyzed. After intraperitoneal transfer (i.p.) of 2 x 10(7) bovine PBL i nto SCID mice, FAGS analysis revealed successful engraftment of bovine CD4( +) and CD8(+) T cells in the peritoneal cavity, the peripheral blood, splee n, lymph nodes, bone marrow, and thymus of reconstituted mice for up to 13 weeks. As shown by immunocytochemistry in sections of spleens from SCID mic e 16 weeks after substitution, bovine T and B cells were localized perivasc ulary forming pseudofollicular structures. Nevertheless, histopathology of spleen and liver from bovine PBL SCID mice revealed pathological alteration s indicating rejection of xenogenic cells or graft versus host disease (GVH D). On the functional level, i.p. transfer of bovine PBL into SCID mice ind uced increasing levels of bovine IgM and IgG in the sera of recipients. Bov ine Ig could be detected up to 20 weeks. Immunization of SCLD mice reconsti tuted with PBL of normal donors with dinitrophenol (DNP)-edestin induced a weak specific bovine antibody response in recipient mice. In contrast, a se condary specific bovine IgG response was observed after antigen restimulati on of SCID mice reconstituted with PBL from calves preimmunized either with DNP-edestin or keyhole limpet hemocyanin (KLH) showing functional T cell-i ndependent and -dependent antibody responses of bovine PBL SCID mice. Our d ata demonstrate that transfer of bovine PBL into SCLD mice leads to a long term engraftment of bovine cells in lymphatic and non-lymphatic organs indu cing a functional substitution of T and B cell immune response of SCID mice . Therefore, bovine PBL SCID chimera can serve as a small animal model for the analysis of bovine lymphopoiesis and infectious diseases of cattle. (C) 1999 Elsevier Science B.V. All rights reserved.