PECULIAR IMMUNOBIOLOGY OF BONE MARROW ALLOGRAFTS

F1 hybrid mice are capable of rejecting inbred parental strain bone marrow grafts after a single lethal exposure to X-rays. The incompatibility is genetically controlled by the Hybrid-histocompatibility-1 (Hh-1) locus in or near the D end of the Histocompatibility-2 (H-2) region. The onset of parental graft rejection begins 9–12 hr after transplantation and is completed by 24 hr. Maturation of hybrid resistance does not occur until the 22nd day of life. In adults, the resistance to parental marrow grafts can be temporarily abrogated or weakened by administration of cyclophosphamide or dead cultures of Corynebacterium parvum, acute supralethal exposures to radiation, or by split-dose irradiation with 6–37-day intervals. Parental marrow grafts elicit a transplantation reaction in irradiated F1 mice which is indistinguishable from that elicited in irradiated allogeneic (H-2-incompatible) hosts. Because of this immunogenetic similarity, the following question is raised: are the same or different alloantigens responsible for rejection of parental and allogeneic marrow grafts? In the first case, Hh-1 alleles would be recessive determinants of tissue-specific transplantation antigens, whereas in the second case they would be the determinants of parental- and tissue-specific antigens subject to genetic suppression in Hh-1 heterozygotes. Although the available evidence is not conclusive in excluding one of the two possibilities, it favors the concept that allograft reactivity to hemopoietic cells is elicited by recessive tissue-specific antigens.

[1]  E. Lotzová,et al.  HYBRID RESISTANCE TO PARENTAL NZW BONE MARROW GRAFTS: Association with the D End of H-2 , 1971, Transplantation.

[2]  M. Bennett,et al.  PECULIAR IMMUNOBIOLOGY OF BONE MARROW ALLOGRAFTS , 1971, The Journal of experimental medicine.

[3]  E. Lotzová,et al.  Genetic Determinants of Hybrid Resistance in Murine Linkage Group IX1 , 1971 .

[4]  G. Cudkowicz.  GENETIC CONTROL OF BONE MARROW GRAFT REJECTION , 1971, The Journal of experimental medicine.

[5]  R. Shadduck,et al.  The effect of preirradiation of recipient mice on the proliferation of transplanted hemopoietic stem cells. , 1971, Blood.

[6]  G. Habicht,et al.  Kinetic Differences in Unresponsiveness of Thymus and Bone Marrow Cells , 1971, Science.

[7]  W. Fried,et al.  Accelerated regeneration of transplanted hematopoietic stem cells in irradiated mice pretreated with cyclophosphamide. , 1971, Blood.

[8]  M. Bennett.  GRAFT-VERSUS-HOST REACTIONS IN MICE: I. KINETIC AND IMMUNOGENETIC STUDIES OF ALLOANTIGENSENSITIVE UNITS OF LYMPHOID TISSUE , 1971, Transplantation.

[9]  H. Claman,et al.  THYMUS-MARROW IMMUNOCOMPETENCE: IV. The Growth and Immunocompetence of Transferred Marrow, Thymus, and Spleen Cells in Parent and F1 Hybrid Mice , 1969, Transplantation.

[10]  D. Metcalf,et al.  Hemopoietic progenitor cells of W anemic mice studied in vivo and in vitro , 1968, Journal of cellular physiology.

[11]  J. Trentin,et al.  HEMOPOIETIC COLONY STUDIES , 1968, The Journal of experimental medicine.

[12]  G. Cudkowicz.  The immunogenetic basis of hybrid resistance to parental marrow grafts. , 1965, The Wistar Institute symposium monograph.

[13]  G. Cudkowicz,et al.  Induction of Immunity and of Unresponsiveness to Parental Marrow Grafts in Adult F1 Hybrid Mice , 1964, Nature.

[14]  G. Cudkowicz,et al.  DEFICIENT GROWTH OF C57BL MARROW CELLS TRANSPLANTED IN F1 HYBRID MICE. ASSOCIATION WITH THE HISTOCOMPATIBILITY-2 LOCUS. , 1964, Immunology.

[15]  J. Till,et al.  Repression of colony-forming ability of c57bl hematopoietic cells transplanted into non-isologous hosts. , 1963 .

[16]  F. Celada,et al.  Demonstration of F1 hybrid anti-parent immunological reaction. , 1962, Proceedings of the National Academy of Sciences of the United States of America.

[17]  G. Snell,et al.  Histocompatibility genes of mice. III. H-1 and H-4, two histocompatibility loci in the first linkage group. , 1961, Immunology.

[18]  G. Cudkowicz.  Evidence for Immunization of F1 Hybrid Mice Against Parental Transplantation Antigens , 1961 .

[19]  G. Snell,et al.  Histocompatibility genes of the mouse. II. Production and analysis of isogenic resistant lines. , 1958, Journal of the National Cancer Institute.

[20]  O. Frankfurt.  [The genetics of tissue transplantation]. , 1961, Patologicheskaia fiziologiia i eksperimental'naia terapiia.