Ralph J. Graff

The influence of the gonads and adrenal glands on the immune response to skin grafts.

Summary The congenic strain pair C57BL/10Sn and BIO-129 (12M) differ from one another at the histocompatibility-12 (H-12) locus. Earlier work has shown that in this strain pair females reject allografts more consistently and more rapidly than males. This study is concerned with the effects of gonadectomy and adrenalectomy on the rejection by preimmunized B10-129(12M) mice of C57BL/10Sn skin allotransplants. Immunized unoperated or sham operated females showed, as expected, a higher per cent of rejections and a shorter rejection time than the comparable male group. Oonadectomy, adrenalectomy, and combined orchiectomy-adrenalectomy substantially increased the strength of rejection of males and, to a lesser extent, the strength of rejection of females. Adrenaleetomizcd and gonadectomized- adrenalectomized males and females showed essentially similar rejection patterns. Following gonadectomy alone, the per cent of rejections by females was higher than the corresponding male group, but the rejection rate was slower. Transplanting testes into oophorcctomized females had a greater effect than transplanting ovaries into orchiectomized males. Oophorectomized females with transplanted testes showed a significantly smaller rejection per cent than oophorectomized females without transplants. In contrast, orchiectomized males receiving transplanted ovaries showed a per cent of rejection not significantly different from orchiectomized males without transplants, although the rejection pattern of the rejecting portion was significantly slower than that of the male orehieetomy group

Histocompatibility genes of mice. VI. Allografts in mice congenic at various non-H-2 histocompatibility loci.

Using a panel of congenic resistant mice differng from C57BL/10ScSn at the H-1, H-3, H-4, H-7, H-8, H-9, H-10, H-11, H-12, and H-13 histocompatibility loci, the median survival times of skin allografts from and to C57BL/10ScSn were obtained. The following observations were made: 1. The strengths of the barriers imposed by the non-H-2 histocompatibility loci were quite variable, the median survival times for the various loci ranging from 15 to > 300 days. 2. The reciprocal graft rejections across non-H-2 burriers were often quite differet. BIOBY mice rejected C57BL/10ScSn skin with a median survival time of 15 days. C57BL/10ScSn mice rejected B10BY skin with a median survival time > 250 days. 3. The longer the median survival time, the greater was the range in survival times of individual grafts. 4. The rejection time of females of a given strain was frequently shorter than that of males. 5. Preimmunization with donor thymocytes increased survival of recipients of tumor allografts and, except in the case of the weakest histocompatibility differences, shortened the survival of skin allografts. 6. Injection at intervals of 1 week of 1, 2, and 4 X 105 thymocytes was less effective in protecting against a subsequent tumor allograft than 10 times these numbers of cells. However, an additional increase the cell dosage did not further increase the protection. 7. Skin grafted 7 days after immunization was rejected faster than skin grafted 14 days after immunization. Skin grafted after triple immunization was rejected faster than skin grafted after single immunization. 8. The strengths of rejection of skin and tumor across non-H-2 histocompatibility barriers paralleled one another.

The cumulative effect of histocompatibility antigens.

SUMMARYIn order to study the cumulative effect of mouse histocompatibility antigens, donor-host combinations were utilized which differed at 2, 3, 4, and multiple histocompatibility loci. Double difference pairs involving the Y-linked and one of several autosomal loci were produced by grafting from

Prolongation of murine skin allografts by prostaglandin e.

The effects of 16,16-dimethyl prostaglandin E2 methyl ester (di-M-PGE2) and indomethacin (an inhibitor of endogenous prostaglandin biosynthesis) on mouse skin allograft survival were studies in B10.D2 female mice receiving skin allografts from (B10.BR X B10.D2)F1 mice. Control animals with and without i.p. diluent injections had a mean allograft survival of 13.8+/-0.6 and 13.5+/-0.5 days, respectively. Daily administration of di-M-PGE2 (200 microng/kg) prolonged mean allograft survival, both when administered alone, 16.7+/-0.6 days (P less than 0.001), or with indomethacin, 4 mg/kg thrice weekly, 16.0+/0.6 days (P less than 0.005). Increasing concentrations of indomethacin (4, 6, and 8 mg/kg thrice weekly) were inversely corrleated with allograft survival ((12.7+/-0.2, 11.8+/-0.2, and 10.9+/-0.4 days, respectively), coefficient of correlation=-0.6986; P less than 0.001. Mean plasma PGE levels at the time of total allograft rejection were 879+/-80 pg/ml in control, 717+/-59 pg/ml in 100 micron g of indomethacin-treated mice, and 654+/-59 pg/ml in 200 microng of indomethacin-treated mice (P less than 0.05). Exogenous di-M-PGE2 prolonged skin allograft survival in mice. Inhibition of endogenous prostaglandin biosynthesis by indomethacin chortened allograft survival, but this effect was completely abrogated by concurrent injection of di-M-PGE2.

Histocompatibility genes of mice. XI. Evidence establishing a new histocompatibility locus, H-12, and new H-2 allele, H-2bc.

SUMMARY Strain B10.129(12M) is a congenic resistant strain differing from its partner strain, C57BL/10 or B10, by a rather weak histocompatibility locus. The locus is unusual in that the sex difference in the response to grafts is especially pronounced. Preimmunized females are strongly resistant to skin or tumor transplants; preimmunized males are not. Evidence presented herewith shows that B10.129(12M) identifies a new histocompatibility locus. This already has been provisionally designated H‐12; this usage is now confirmed. The allele of B10.129(12M) is assigned the symbol H‐12b. Congenic resistant strain B10. 129(6M) is also H‐12b but in addition carries a minor H‐2 difference from B10. Strain B10 is H‐2b; strain B10. 129(6M) has a new H‐2 allele, derived from the 129 parental strain, to which the symbol H‐2bc is assigned. Strain B10. 129(6M), unlike B10, also reacts with TL antisera. Presumably the Tla allele of 129, which determines the TL.2 antigen, was brought in with the H‐2 allele to which it is closely linked.

HISTOCOMPATIBILITY GENES OF MICE: IX. The Distribution of the Alleles of the Non-H-2 Histocompatibility Loci1

SUMMARY A panel of commonly used inbred mouse strains was typed for the alleles of the H‐1, H‐3, H‐4, H‐7, H‐8, H‐9, H‐12, and H‐13 histocompatibility loci using histogenetic techniques. Typing revealed new alleles at all loci with the exception of H‐1. Because of the inability to type for the null antigen of the H‐1b allele, we could not distinguish between strains possessing H‐1b and those possessing new alleles. The strengths of the non‐H‐2 antigens varied from the relatively strong H‐1c antigen to the extremely weak H‐9b antigen. The immune response of 3 F1 groups, CBA/J, DBA/2J, and DBA/1Sn × CR partner, appeared weaker than that of the remaining groups. In general, related strains showed fewer histocompatibility differences than unrelated strains.

HISTOCOMPATIBILITY GENES OF MICE VIII. THE ALLELES OF THE H-1 LOCUS

SUMMARYA panel of congenic resistant strains, B10.BY, B10.129(5M), B10.C(41N), B10.C3H(40NX), and B10.D2(58N), were found to differ from their background strain, C57BL/10, at the H-1 locus. These strains were typed for the a, b, and c, alleles of the H-1 locus using C3H (H-1a), C3H.K (H-1b), and C57

Immunogenic properties of papain-solubilized h-2 alloantigens.

SUMMARY The immunogenic properties of papain-solubilized alloantigen preparations from C57EL/6.I and BALB/c+I spleen cells were studied. Doses of 2.S-50 μg of protein, administered with Freunds adjuvant, accelerated skin graft rejection across H-2 barriers. In addition, BALB/cJ preparation was shown to possess non-H-2 activity. The i.v. injection of single and multiple doses of the C57BL/6J preparation did not prolong graft survival. Some groups even showed accelerated rejection.

Considerations in the treatment of traumatic hemobilia.

Abstract 1. 1. The first uses of preoperative hepatic arteriography and radioactive rose bengal hepatoscan in traumatic hemobilia are reported. 2. 2. The surgical management of traumatic hemobilia, based upon results in all cases reported to date, is preliminarily evaluated. In general, hemobilia secondary to central and subcapsular ruptures of the liver has responded well to drainage of the cavity plus decompression of the extrahepatic biliary tract; whereas, hemobilia following persistent bleeding from liver lacerations has usually required more radical procedures for hemostasis.

Estimates of histocompatibility differences between inbred mouse strains.

The targets of allograft rejection have been shown to be under the control of multiple histocompatibility (H) genes. Using the murine model, scientists have attempted to estimate the number of genes by which various strain pairs differ. Early estimates based on the percentage of rejection of parental strain skin grafts by F 2 and/or backcross mice were in the range of 14 to 17 (Little and Tyzzer 1916, Barnes and Krohn 1957, Prehn and Main 1958). These techniques suffered from two shortcomings: (1) because of the large number of H genes by which the parental strains differed, very few grafts were accepted and the resultant error was great, and (2) the technique allowed only one opportunity for crossover; therefore, multiple closely linked H genes behaved as one gene and the estimates were small. Bailey and Mobraaten (1969) minimized these two shortcomings by basing their estimates on the survival of skin grafted between partially inbred mice and from multiply backcrossed mice to parental strain mice. In both cases the number of surviving skin grafts and the opportunities for crossovers were increased manyfold. Using these techniques Bailey and Mobraaten estimated that strains BALB/cBy and C57BL/6By differ by 28 or 29 H genes. Brambilla et al. (1970) used fewer reductional matings and a prolonged observation period to increase the sensitivity of their system. They estimate that strains C57BL/6 and DBA/2 differ by 36 H genes (28 based on rejection by male recipients, 44 based on rejection by female recipients). In this study we have estimated the H differences between strain combinations C57BL/6J and DBA/2J, C57BL/6J and C3H/HeJ, and B10.D2/n and DBA/2Grf using the techniques described by Bailey and Mobraaten (1969) and extending the interval of observation. In addition, we have increased the sensitivity of the system by preimmunizing male graft recipients in the B10.D2/n and DBA/2JGrf combination, resulting in an estimate of 88 H-gene differences.