Recipient Phenotype Research Articles

Temporal replacement of donor erythrocytes and leukocytes in nonanemic W44J/W44J and severely anemic W/Wv mice

The dominant white spotting, W, locus in the mouse encodes Kit, a receptor molecule with cytosolic tyrosine kinase activity. Mutations in Kit deplete hematopoietic cells by an as yet unknown mechanism, but one that presumably affects the early progenitors of all cell lineages. To examine cell lineage-specific changes caused by different W mutations, we injected genetically marked normal marrow cells into mutant mice and monitored repopulation kinetics. In the present report, we compare repopulation of the various peripheral blood cells in nonanemic W44J/W44J and severely anemic W/Wv mice administered increasing increments of donor cells. At all doses of cells tested, donor erythrocyte repopulation precedes leukocyte repopulation regardless of the recipient phenotype. There is, in fact, little difference in the rate or extent of nonerythroid repopulation in W44J/W44J mice injected with between 6 x 10(6) and 2 x 10(7) donor cells. The fact that donor cells rapidly replace erythrocytes, even in the nonanemic W44J/W44J host, while other cell lineages become donor type more slowly provides further evidence that mutations at the W locus are especially damaging to erythrocyte progenitors. We suggest that host nonerythroid hematopoietic cells compete with normal cells, probably at the level of early progenitors rather than at the level of the totipotent hematopoietic stem cell. The fact that successively higher doses of donor cells do not markedly alter nonerythroid repopulation kinetics implies that it may be possible to maximize autologous therapeutic marrow transplantation.

Temporal Replacement of Donor Erythrocytes and Leukocytes in Nonanemic W44J/W44J and Severely Anemic W/Wv Mice

Abstract The dominant white spotting, W, locus in the mouse encodes Kit, a receptor molecule with cytosolic tyrosine kinase activity. Mutations in Kit deplete hematopoietic cells by an as yet unknown mechanism, but one that presumably affects the early progenitors of all cell lineages. To examine cell lineage-specific changes caused by different W mutations, we injected genetically marked normal marrow cells into mutant mice and monitored repopulation kinetics. In the present report, we compare repopulation of the various peripheral blood cells in nonanemic W44J/W44J and severely anemic W/Wv mice administered increasing increments of donor cells. At all doses of cells tested, donor erythrocyte repopulation precedes leukocyte repopulation regardless of the recipient phenotype. There is, in fact, little difference in the rate or extent of nonerythroid repopulation in W44J/W44J mice injected with between 6 x 10(6) and 2 x 10(7) donor cells. The fact that donor cells rapidly replace erythrocytes, even in the nonanemic W44J/W44J host, while other cell lineages become donor type more slowly provides further evidence that mutations at the W locus are especially damaging to erythrocyte progenitors. We suggest that host nonerythroid hematopoietic cells compete with normal cells, probably at the level of early progenitors rather than at the level of the totipotent hematopoietic stem cell. The fact that successively higher doses of donor cells do not markedly alter nonerythroid repopulation kinetics implies that it may be possible to maximize autologous therapeutic marrow transplantation.

Effect of the number of pregraft blood transfusions in kidney graft recipients treated with bioreagents and cyclosporin A

The impact of a systematic, nondonor-specific, pregraft blood transfusion (BT) protocol was evaluated retrospectively in 446 consecutive, first renal transplant recipients with regard to graft survival rate, rejection, and incidence of infectious episodes. Cyclosporin A was the maintenance immunosuppressive treatment in all patients after a 2-week course of antithymocyte globulin or anti-IL-2 monoclonal antibody. Recipients were assigned to three groups according to the number of pregraft BT (one or two, three or four, or more than four). When nonimmunological failures were excluded from the study, patients receiving three or four BT had statistically better graft survival (P less than 0.02) and a lower incidence of rejection episodes (P less than 0.05) than those in the other groups. There were no significant differences between the three groups in the distribution of HLA mismatching (A, B and DR), time interval between the last BT and transplantation, DR6 recipient phenotype, or nonimmunological failures. Our results show that the number of pregraft BT is an important factor in transplantation.

Effect of the number of pregraft blood transfusions in kidney graft recipients treated with bioreagents and cyclosporin A

Abstract. The impact of a systematic, nondonor-specific, pregraft blood transfusion (BT) protocol was evaluated retrospectively in 446 consecutive, first renal transplant recipients with regard to graft survival rate, rejection, and incidence of infectious episodes. Cyclosporin A was the maintenance immunosuppressive treatment in all patients after a 2-week course of antithymocyte globulin or anti-IL-2 monoclonal antibody. Recipients were assigned to three groups according to the number of pregraft BT (one or two, three or four, or more than four). When nonimmunological failures were excluded from the study, patients receiving three or four BT had statistically better graft survival (P < 0.02) and a lower incidence of rejection episodes (P < 0.05) than those in the other groups. There were no significant differences between the three groups in the distribution of HLA mismatching (A, B and DR), time interval between the last BT and transplantation, DR6 recipient phenotype, or nonimmunological failures. Our results show that the number of pregraft BT is an important factor in transplantation.

The Evolution of Conspecific Acceptance Thresholds

The differential treatment of conspecifics (e.g., kin recognition) has three components. (1) The production component refers to the nature of the cues used by an individual (actor) to discriminate among classes of conspecifics (recipients) differing in their effects on the actor's fitness. (2) The perception component refers both to the internal template against which the actor matches these cues and to the matching algorithm that allows classification of a recipient (Sherman and Holmes 1985). I introduce a third component, (3) the action component, which refers to the determinants of an action taken by an actor that has calculated a particular degree of similarity between its internal template and a recipient's phenotype. I attempt to provide a theory of the action component of conspecific discrimination. In particular, I examine the factors that determine the optimal or evolutionarily stable acceptance threshold, that is, the level of dissimilarity between the actor's template and the recipient's phenot...

Progressive Replacement of Human Cultured Epithelial Allografts by Recipient Cells as Evidenced by HLA Class I Antigens Expression

Human keratinocytes may be grown in vitro into living epithelia devoid of Langerhans cells and MHC class II antigens. These epithelia have been shown to be usable as epidermal allografts in patients with dermal wounds, without any apparent sign of rejection in the 12-month follow-up study. To evidence a progressive replacement by recipient cells of the grafted keratinocytes, we employed anti-MHC class I antigen monoclonal antibodies directed against tissue specificities expressed by either donors or recipients. At 2 and 4 weeks after grafting, some small epithelial cell islets from the recipient phenotype were clearly identified among cells from a donor origin by indirect immunofluorescence. At 6 months, all keratinocytes present at the grafted areas were labelled by antibodies directed toward recipient specificities only. This replacement may be related to the fact that, when placed on such superficial dermal wounds, the allografts are likely colonized by epithelial cells proliferating from residual recipient dermal appendages.

Possible alteration of normal mechanisms of endotoxin toxicity in vivo by actinomycin D.

The effect of actinomycin D on the sensitivity of endotoxin-responsive (C3HeB/FeJ) and endotoxin-unresponsive (C3H/HeJ) mice to challenge with purified lipopolysaccharide (LPS) of Escherichia coli strain O55:B5 was examined using an experimental protocol of adoptive transfer of lymphoid cells into lethally irradiated recipients. Earlier results--that in the absence of actinomycin D, the ability of LPS to cause a lethal response in the immunologically chimeric mice reflected the phenotypic response of the donor lymphoid cells--were confirmed. Simultaneous administration of actinomycin D to endotoxin-responsive C3HeB/FeJ mice increased by several orders of magnitude the sensitivity of these mice to the lethal effects of LPS. Determinations of 50% lethal doses in the presence of actinomycin D indicated that immunologic chimeras were sensitive to lethal effects of LPS if either the donor or the recipient phenotype was LPS-responsive. Thus, the mechanism(s) of host response to LPS in the presence of actinomycin D may not be identical to those elicited in untreated mice.