Allogenicity

Abstract: Laboratory strains of mice are thought to be derived from wild populations of Mus domesticus. Many instances of non-domesticus genetic information fixed in these strains have been described, however, and the amount of strain-to-strain genetic variation exceeds that found in wild domesticus populations. In order to estimate the extent of the non-domesticus contribution to laboratory mouse genomes, and to determine whether it could account for observed variation, we have used computer simulations to investigate the properties of genetically marked chromosomal segments and the distribution of residual allogenicity at various times during inbreeding. A locus or chromosomal segment is allogenic if it is unfixed within a lineage at a given time. The odds of fixation of a foreign chromosome segment are predicted to be an exponentially decreasing function of its length. The median segment length is predicted to be 17 centimorgans. Available data for markers of chromosomes 1, 9 and 12 in recombinant inbred strain sets conform to these predictions. Together, the results suggest that introgression of non-domesticus chromosomes and segregation of residual allogenicity are sufficient to account for the genetic diversity observed among inbred mouse strains and substrains.

Abstract: The HistoCheck1 software is offered as a tool 'that is capable of assessing the allogenicity (matching score) between any pair of clinically relevant HLA class I... alleles'. This is a brave attempt to aid Transplant Physicians in making the often difficult choice between two or more mismatched (unrelated) donors, when no completely matched donor is available. This internet-based software provides a score that takes into account both the functional and the structural difference between two HLA alleles at one locus. The predictive value of HistoCheck is based on the presumption that transplant success is improved by selecting a donor with an HLA type most similar to the patient.

Abstract: The development of regenerative medicine relies in part on the capacity of stem cells to differentiate into specialized cell types and reconstitute tissues and organs. The origin of the stem cells matters. While autologous cells were initially the preferred ones the need for "off the shelf" cells is becoming prevalent. These cells will be immediately available and they originate from young non diseased individuals. However their allogenicity can be viewed as a limitation to their use. Recent works including our own show that allogenicity of stem cell can be viewed as on one hand detrimental leading to their elimination and on the other hand beneficial through a paracrine effect that can induce a local tissue regenerative effect from endogenous stem cells. Also their immune modulatory capacity can be harnessed to favor regeneration. Therefore the immune phenotype of stem cells is an important criteria to be considered before their clinical use. Immuno monitoring of the consequences of their in vivo injection needs to be taken into account. Transplantation immunology knowledge will be instrumental to enable the development of safe personalized regenerative stem cell therapy.

Abstract: Lymphocytes obtained from mesenteric lymph nodes of rabbits were stimulated in vitro by concanavalin A and injected into the corneas of allogeneic hosts. Controls were nonstimulated, killed, or autogeneic lymphocytes injected into the contralateral corneas. The stimulated cells were significantly better inducers of neovascular growth. Histologic observations of the vascularized corneas showing marked mononuclear reactions at the limbus, coupled with the requirement of allogenicity, suggest that there was immunologic recognition of the implanted cells. Stimulated allogeneic blast cells may amplify this host recognition by their elaboration of lymphokines or enhanced antigenicity. The apparent importance of allogenicity for the induction of vessel growth in these experiments may be significant in the pathogenesis of tumorinduced or graft-related corneal neovascularization.