Hybrid immune response to parental liver tissue grafts

Parental-to-F 1 -hybrid liver tissue grafts in like-sex donor-recipient combinations survive indefinitely, although several F 1 recipients demonstrate an immunological response to the parental graft. Female F 1 recipients, particularly those carrying the H-2 b haplotype, respond vigorously to male parental liver grafts. However F 1 female responses to male parental liver tissue grafts differ substantively from the responses of parental females to syngeneic male grafts. C3H male liver grafts are rejected vigorously by F 1 females as long as the F 1 carries the H-2 b haplotype. These findings support previous reports of strong immunological responses to C3H H-Y antigen in female F 1 and C3H.SW animals, a response which is absent in C3H females. Female F 1 hybrids carrying the H-2 b haplotype do not reject grafts of B10 or B6 male liver as rapidly as do B10 or B6 parental females. This reduced F 1 response may be related to the formation of hybrid antigens and consequent alteration of the anti-H-Y response. Alternatively, cells that specifically suppress the anti-H-Y response may be present in F 1 hybrids. Factors responsible for suppression appear to be controlled by non-MHC antigens, at least in (OH x B6 or B10) F 1 hybrids.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46740/1/251_2004_Article_BF00696870.pd

Tissue graft rejection in mice

A tissue slice-to-kidney bed grafting system is used to study the mechanism of specific tissue rejection (in this case, rejection of liver tissue) over a series of histocompatibility barriers other than the H-2 barrier. Using the method described, it is possible to obtain a pattern or time-course picture of the immunological process, rather than a mean survival time. It is clear from histological observations of these patterns that, although there are considerable differences in numbers of liver grafts which survive for long period's across the several histocompatibility barriers studied, some grafts in almost every case survive the immunological challenge elicited by the genetic barriers. Grafts of liver tissue are therefore similar, but not identical, in survival patterns to grafts of tumor, ovary, and skin. These studies also indicate that immunological mechanisms controlling rejection of tissue over H barriers other than H-2 differ from those controlling rejection over the major histocompatibility barrier in the mouse.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46754/1/251_2005_Article_BF01563948.pd

Tissue graft rejection in mice

The influence of H-2 subregions on graft survival in a liver slice-tokidney bed grafting system has been investigated. H-2K -region and H-2IA -region donor-recipient differences, either individually or in concert, cause acute graft rejection. H-2D -region donor-recipient differences cause chronic immunological reaction as evaluated by histological criteria. Grafts across this barrier may ultimately be rejected or may survive indefinitely. Several possible explanations for the variation in survival are proposed. The remaining known H-2 regions ( IB, IC, S , and G ) all appear to cause immunological reactivity in a recipient animal which differs from the liver tissue donor at any of these regions. However, only an IC -region difference may ultimately cause complete graft destruction following an extended chronic immunological course. Grafts across background histocompatibility barriers of several genetic types show rejection patterns equivalent to those seen across K and IA barriers. These patterns are unchanged, whether or not the donor and recipient are congenic for H-2 alleles. Different H-2 allelic donor-recipient differences do, however, show different times of survival, indicating variation in strength or number of donor antigens or differences in recipient immune response.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46752/1/251_2005_Article_BF01575670.pd

H-2 and Background influences on tissue grafts across the H-Y barrier

Male liver was grafted to kidney beds in syngeneic female mice. Relative influences of H-2 haplotype, genetic background or interaction of H-2 haplotype with genetic background on anti-H-Y response were evaluated using 27 inbred strains carrying eight H-2 haplotypes of independent origin and three naturally occurring recombinants. Females of H-2 b haplotype acutely rejected the male graft as is reported for other tissue graft systems. An H-2 haplotype influence was found for all haplotypes studied, with a greater variation of immunologic response revealed by histological analysis of liver grafts than is demonstrated by skin grafts. Strains carrying H-2 k , H-2 j and H-2 p haplotypes expressed the greatest range of immunological variability with responses ranging from graft proliferation to graft rejection. Strains carrying the H-2 d haplotype had the most consistent responses with little reaction to the graft. The strong immune response by SJL/J ( H-2 s ) female mice to the H-Y antigen is not typical of other H-2 s strains, but is compatible with the reported hyperresponsiveness of this strain to alloantigens.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46755/1/251_2005_Article_BF01570432.pd

Growth Hormone (GH) Secretion in Primary Adrenal Insufficiency: Effects of Cortisol Withdrawal and Patterned Replacement on GH Pulsatility and Circadian Rhythmicity

We studied the effects of cortisol withdrawal and patterned replacement upon spontaneous GH secretion and circadian rhythmicity in 7 patients with Addison's disease. Hydrocortisone was administered in physiological daily total dosages, and all resulting plasma cortisol values were 2–15 μg/dl. It was given in 3 pulsatile modes: simulating “physiological” rhythm, “reverse” diurnal rhythmicity and “continuous” pulsatility. All modes of cortisol administration increased mean 24h, GH pulse amplitude and interpulse GH levels. During saline infusions circadian GH rhythmicity was preserved, with GH being at its highest between 2400–0400 h. Administration of hydrocortisone in any mode did not modify circadian GH rhythmicity. We conclude: Cortisol replacement in physiological daily doses increases GH output in patients with Addison's disease by augmenting GH pulse amplitude and interpulse levels. This is likely due to the attenuation of hypothalamic somatostatin (SRIF) secretion by physiologic levels of cortisol. By inference, it implies that cortisol deficiency leads to diminution of GH output with low GH pulse amplitude, likely as a result of an augmented hypothalamic somatostatin secretion. However, circadian rhythmicity of GH secretion is glucocorticoid-independent.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47487/1/11102_2004_Article_324056.pd

Immunogenetic control of the response of female mice to male tissue grafts

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46736/1/251_2005_Article_BF01561664.pd

Liver tissue graft rejection in murine major histocompatibility complex mutants

Liver tissue grafts between seven H-2 mutants and their parental strains have been studied. Each of these mutants was originally identified by reciprocal mutant—parental strain skin graft rejection. However, liver grafts among mutants and parental standard strains are not uniformly rejected. Liver graft rejection also fails to correlate with mutant—parental stimulation in CML and MLC. In addition, the immune reaction pattern of female mutant animals against grafts of male liver differs from the reaction pattern found in parental standard strains. Several explanations for the differences between immune response to liver and skin grafts are proposed, including different T cell subsets involved in recognition, availability of antigenic sites to immunocompetent cells, and structural differences between mutant and parental H-2 antigens.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46738/1/251_2004_Article_BF00364259.pd