Bone Marrow Graft Rejection as a Function of TNK Cells

  • Gunther Dennert


Almost three decades ago, G. Cudkowicz (Cudkowicz and Cosgrove, 1961) made the curious observation that irradiated (A × B)F1 hybrid mice transplanted with parental bone marrow from either parent A or parent B may acutely reject one but not the other graft. The observation was unexpected, as transplantation antigens are known to be inherited codominantly (Snell, 1953) and therefore parental marrow grafts should not be subject to immunological rejection mechanisms. He subsequently postulated that the antigenic determinants recognized during the rejection are expressed on parental and not on F1 hybrid cells and hence must be inherited noncodominantly (Cudkowicz and Stimpfling, 1964). The antigens were named hemopoietic histocompatibility (Hh) antigens (Cudkowicz, 1971; Cudkowicz and Lotzova, 1973) and genetic studies revealed that they often encoded close to the major histocompatibility complex (MHC) region. For example, the resistance of (C57BL/6 × C3H)F1 mice to C57BL/ 6 marrow was mapped to the D region of the MHC (Cudkowicz and Stimpfling, 1964b). Perhaps not surprisingly, the phenomenon of acute parental marrow graft rejection in F1 hybrid mice, also called hybrid resistance (HR), found its counterpart in the ability of irradiated mice to acutely reject allogeneic marrow grafts (Cudkowicz and Bennett, 1971a). Again, the specificity of acute allogeneic marrow graft rejection pointed to antigenic determinants that were encoded close to the MHC region. As examples of this, the rejection of H-2d marrow by C57BL/6 mice maps to the D region of the MHC (Cudkowicz and Stimpfling, 1964b; Cud-kowicz, 1975a), and the rejection of H-2k marrow by strain 129 mice maps to the K region (Cudkowicz and Warner, 1979). The two mouse strains 129 and C57BL/6 which are of H-2b haplotype, provide an interesting experimental model because they show opposing responsiveness to H-2d and H-2k marrow grafts (Cudkowicz, 1975a; Cudkowicz and Warner, 1979). C57BL/6 fails to acutely reject H-2k marrow, and 129 is a nonresponder for H-2d marrow.


Natural Killer Natural Killer Activity Hybrid Mouse Marrow Graft Hybrid Resistance 
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© Birkhäuser Boston 1993

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  • Gunther Dennert

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