NK cell tolerance in mixed allogeneic chimeras

Alterations in inhibitory receptor expression on NK cells have been detected in mixed allogeneic chimeras and in mosaic MHC class I-expressing transgenic mice. However, it is not known whether or not NK cells are tolerant to host and donor Ags in mixed chimeras. In vitro studies have shown a lack of mutual tolerance of separated donor and host NK cells obtained from mixed chimeras. Using BALB/c-->B6 fully MHC-mismatched mixed chimeras, we have now investigated this question in vivo. Neither donor nor host NK cells in mixed chimeras showed evidence for activation, as indicated by expression of B220 and Thy-1.2 on NK cells in chimeric mice at levels similar to those in nonchimeric control mice. Lethally irradiated, established mixed BALB/c--> B6 chimeras rejected a low dose of beta(2)-microglobulin-deficient bone marrow cells (BMC) efficiently but did not reject BALB/c or B6 BMCs. In contrast, similarly conditioned B6 mice rejected both BALB/c and beta(2)-microglobulin-deficient BMCs. Thus, NK cells were specifically tolerant to the donor and the host in mixed allogeneic chimeras. The similar growth of RMA lymphoma cells in both chimeric and control B6 mice further supports the conclusion that donor BALB/c NK cells are tolerant to B6 Ags in chimeras. Administration of a high dose of exogenous IL-2 could not break NK cell tolerance in chimeric mice, suggesting that NK cell tolerance in chimeras is not due to a lack of activating cytokine. No reduction in the level of expression of the activating receptor Ly-49D, recognizing a donor MHC molecule, was detected among recipient NK cells in mixed chimeras. Thus, the present studies demonstrate that NK cells in mixed chimeras are stably tolerant to both donor and host Ags, by mechanisms that are as yet unexplained.     

Development of either split tolerance or robust tolerance along with humoral tolerance to donor and third-party alloantigens in nonmyeloablative mixed chimeras

Hematopoietic chimerism is considered to generate robust allogeneic tolerance; however, tissue rejection by chimeras can occur. This "split tolerance" can result from immunity toward tissue-specific Ags not expressed by hematopoietic cells. Known to occur in chimeric recipients of skin grafts, it has not often been reported for other donor tissues. Because chimerism is viewed as a potential approach to induce islet transplantation tolerance, we generated mixed bone marrow chimerism in the tolerance-resistant NOD mouse and tested for split tolerance. An unusual multilevel split tolerance developed in NOD chimeras, but not chimeric B6 controls. NOD chimeras demonstrated persistent T cell chimerism but rejected other donor hematopoietic cells, including B cells. NOD chimeras also showed partial donor alloreactivity. Furthermore, NOD chimeras were split tolerant to donor skin transplants and even donor islet transplants, unlike control B6 chimeras. Surprisingly, islet rejection was not a result of autoimmunity, since NOD chimeras did not reject syngeneic islets. Split tolerance was linked to non-MHC genes of the NOD genetic background and was manifested recessively in F(1) studies. Also, NOD chimeras but not B6 chimeras could generate serum alloantibodies, although at greatly reduced levels compared with nonchimeric controls. Surprisingly, the alloantibody response was sufficiently cross-reactive that chimerism-induced humoral tolerance extended to third-party cells. These data identify split tolerance, generated by a tolerance-resistant genetic background, as an important new limitation to the chimerism approach. In contrast, the possibility of humoral tolerance to multiple donors is potentially beneficial.     

Tissue specific loss of proliferative capacity of parthenogenetic cells in fetal mouse chimeras

Parthenogenetic cells are lost from fetal chimeras. This may be due to decreased proliferative potential. To address this question, we have made use of combined cell lineage and cell proliferation analysis. Thus, the incorporation of bromodeoxyuridine in S-phase was determined for both parthenogenetic and normal cells in several tissues of fetal day 13 and 17 chimeras. A pronounced reduction of bromodesoxyuridine incorporation by parthenogenetic cells at both developmental stages was only observed in cartilage. In brain, skeletal muscle, heart and intestinal epithelium, this reduction was either less pronounced or observed only at one of the developmental stages analysed. No difference between parthenogenetic and normal cells was observed in epidermis and ganglia. Our results show that a loss of proliferative potential of parthenogenetic cells during fetal development contributes to their rapid elimination in some tissues. The analysis of the fate of parthenogenetic cells in skeletal muscle and cartilage development demonstrated different selection mechanisms in these tissues. In skeletal muscle, parthenogenetic cells were largely excluded from the myogenic lineage proper by early post-midgestation. In primary hyaline cartilage, parthenogenetic cells persisted into adulthood but were lost from cartilages that undergo ossification during late fetal development.     

Implants of quail thymic epithelium generate permanent tolerance in embryonically constructed quail/chick chimeras

In situ implantation of a quail wing bud into a chick embryo at 4 days of incubation (E4) regularly results in the normal development of the implant followed by its acute rejection starting within two weeks post-hatching. If the epithelial thymic rudiments of the quail donor are implanted into the branchial arch area of the chick recipient after partial removal of its own thymic primordia, a chimeric thymus develops in the chick host and this induces tolerance to the quail wing by the chick recipient. The species identity of cells in chimeric thymuses was mapped using Feulgen-Rossenbeck' staining and immunolabelling with monoclonal antibodies directed against quail or chick B-L antigens. Certain lobes contained only chick cells both at the stromal and hemopoietic cell levels. Others had a quail epithelial stroma containing host hemopoietically derived cells. Only chimeras in which at least one third of the thymic lobes were chimeric showed permanent tolerance to the grafted wing. Since the two species exhibit distinct developmental rates, we decided to study the kinetics of thymic involution after birth. Although the changes in thymus weight and histological structure are fundamentally similar in quail and chick, those in the quail start about 7-8 weeks earlier. In the chimeric thymuses, the lobes whose epithelial cells were quail involuted at the rate of control quail showing no influence of the hemopoietic thymic compartment in this process. Tolerance induced by the thymic epithelium during embryogenesis and in early postnatal life was maintained after a profound involution of the quail thymic graft had occurred.     

Urbanisation tolerance and the loss of avian diversity

Urbanisation is considered an important driver of current biodiversity loss, but the underlying causes are not fully understood. It is generally assumed that this loss reflects the fact that most organisms do not tolerate well the environmental alterations associated with urbanisation. Nevertheless, current evidence is inconclusive and the alternative that the biodiversity loss is the result of random mechanisms has never been evaluated. Analysing changes in abundance between urbanised environments and their non‐urbanised surroundings of > 800 avian species from five continents, we show here that although random processes account for part of the species loss associated with urbanisation, much of the loss is associated with a lack of appropriate adaptations of most species for exploiting resources and avoiding risks of the urban environments. These findings have important conservation implications because the extinction of species with particular features should have higher impact on biodiversity and ecosystem function than a random loss.     

Similarity and difference in the mechanisms of neonatally induced tolerance and cyclophosphamide-induced tolerance in mice

The mechanisms of cyclophosphamide (CP)-induced tolerance were investigated by comparing with those of neonatally induced tolerance. When C3H/He Slc (C3H; H-2k, Mls-1b) mice were given i.v. either AKR/J Sea (AKR; H-2k, Mls-1a) or (AKR x C3H)F1 (AKC3F1; H-2k, Mls-1a/b) spleen cells and treated i.p. with CP 2 days later, a long-lasting skin allograft tolerance to AKR was induced in each case without any signs of graft-vs-host disease (GVHD). However, typical signs of GVHD were observed in the C3H mice neonatally tolerized with AKR spleen cells, but not in those tolerized with AKC3F1 spleen cells. The expression of TCR V beta 6, which is strongly correlated with the reactivity to Mls-1a Ag (of donor AKR origin), in the periphery was quite different between the two types of tolerant C3H mice. Namely, in the lymph nodes of the C3H mice tolerized with AKR spleen cells and CP, only CD4(+)-V beta 6+, but not CD8(+)-V beta 6+, T cells selectively disappeared, whereas both of them were abrogated in the lymph nodes of the C3H mice neonatally tolerized of AKR. By contrast, in the thymus of the two types of tolerant C3H mice, both CD4+CD8- and CD4-CD8+ single-positive thymocytes expressing TCR V beta 6 were clonally deleted, suggesting that the thymic involvement was the same in each type of tolerance. These results suggest that the preferential disappearance of the CD4(+)-V beta 6+ T cells (of host origin) and the effector T cells of GVHD (of donor origin) occurred only in the periphery of the C3H mice tolerized with AKR spleen cells plus CP and was attributable to the destruction of Ag-stimulated T cells by the CP treatment. In contrast, the intrathymic clonal deletion of immature V beta 6+ T cells was a common mechanism for both of the tolerance induction systems.     

'Recessive' species-specific antigens in doves and pigeons

Evidence is presented that recessive species-specific antigens are present in pigeons and doves as determined by antiserum absorptions with cells of the opposing parental and Fi birds. This confirms and extends earlier observations by M. R. Irwin and L. J. Cole and adds another species. A simple model is presented postulating a relationship between genes, enzymes, and 'dominant and recessive' antigens.     

Hematologic responses in captive white-winged doves (Zenaida asiatica), induced by various radiotransmitter attachments

White blood cell counts, heterophil-lymphocyte ratios, and leukocyte differentials of captive white-winged doves (Zenaida asiatica) from Texas equipped with different radiotransmitter attachment packages were monitored. Doves were segregated by gender and age by males, females, and hatching year; individuals housed in 30 large outdoor pens in groups of seven. Treatments consisted of controls, glue-on transmitters, body loop harnesses, surgically implanted intracoelomic transmitters, surgically implanted subcutaneous transmitters, intracoelomic surgery without implants, and subcutaneous surgery without implants. We used multivariate analysis of variance with pen as a blocking variable and gender nested and repeated measures analysis of variance to identify differences among any of the transmitter attachment techniques and the control for dependent variables. We found no difference in blood parameters between transmitter attachment technique versus a control.     

Lesion‐induced neurogenesis in the hypothalamus is involved in behavioral recovery in adult ring doves

Although neurogenesis in the brain of adult vertebrates is region dependent, lesion induces generation of new neurons in non‐neurogenic brain regions. These findings raise the question of the role of new neurons in brain repair and functional recovery. We addressed this question by applying previous observations that electrolytic lesion induced neurogenesis in the ventromedial nucleus (VMN) of the hypothalamus in adult ring doves. Such lesions disrupted the male's courtship behavior, which could be reinstated after rehabilitation with a female. We investigated whether lesion‐induced newborn neurons in the VMN facilitate the recovery of courtship behavior in the lesioned birds. We conducted systematic observations of cytological, morphological, and neuroanatomical changes in the lesioned VMN, and concurrently we monitored behavioral changes. Using a multitude of specific cell markers, we found a well‐circumscribed cellular zone that proliferated actively. This highly proliferative zone initially appeared along the periphery of the lesion site, where cells had high levels of expression of neuronal, glial, and neurovascular markers. As newborn neurons matured at the lesion site, the necrosis gradually decreased, whereas a downsized proliferative zone relocated to a region ventral to the VMN. Some of the mature neurons were found to project to the midbrain vocal nuclei. Restoration of these projection neurons coincided with the recovery of courtship vocalization. Finally, we found that a social factor, that is, when the male doves were cohoused with a mate, facilitated neurogenesis and behavioral recovery. These results suggest that lesion‐induced neurogenesis contributes to behavioral recovery in adult animals. © 2006 Wiley Periodicals, Inc. J Neurobiol, 2006     

Genetic constitution of germ cells in intervarietal and interspecific chimeras of Brassica induced by in-vitro grafting

The characteristics of intervarietal and interspecific chimeras synthesized by the graft-culture method were determined by morphology, anthocyanin pigmentation pattern, and crossing. In an intervarietal chimera between YR-ranpou (green cabbage) and Ruby ball (red cabbage) in Brassica oleracea, a segregation phenomenon was noted in which seeds giving rise to purple and green plants were both produced in a single capsule in F₁ progeny from crosses of chimeras with YR ranpou, the anthocyanin-free graft partner type. The degrees of segregation varied, reflecting the structure of the chimeras. YR ranpou-dominant chimeras produced capsules in which seeds gave rise to green plants at a high frequency, while Ruby ball-dominant chimeras produced capsules in which seeds in one capsule gave rise to purple plants at a high frequency. Mixed chimeras produced capsules with green plants or purple plants more regularly than did other chimeral types. Furthermore, a chimeral type in which seeds gave rise to green and purple plants was found in 3.2% of the total crosses. Segregation patterns in the progenies corresponded with the chimeral types. Chlorophyll-deficient variation (resulting in variegation or the production of albino plants) was found at a frequency of 2.6%. These results show that chimeric tissues are actually in a mixed state and that either the ovary develops from more than two cells or else that variation occurs in the germ-cell layer. In interspecific chimeras between Ruby ball and Komatsuna (B. campestris) various types of chimeras generally showed low pollen fertility, few capsules, and low seed-setting. Progenies from selves (geitonogamy), open crosses and crosses with the two parental species produce a predominantly homogeneous genotype showing either the Ruby ball or the Komatsuna type. Only two crosses produced four interspecific hybrids which expressed variations in their morphological and isozymic characters.     

Hybridization and postzygotic isolation patterns in pigeons and doves

Abstract.— The study of the patterns of reproductive isolation in relation to species divergence is critical for the understanding of the process of speciation. Comparative analyses of this kind were previously conducted in Drosophila , Lepidoptera, frogs, ducks, and birds in general. In the present study, we used information from the literature to analyze hybrid inviability in relation to species divergence in pigeons and doves. Four main patterns arose from this analysis: (1) as in the other groups studied, F₁ hybrid inviability gradually increases as species diverge, the time needed to reach total inviability being higher in birds than in the other groups; (2) as expected, the presence of geographic overlap does not influence the evolution of postzygotic isolation; (3) the percentage of unhatched eggs does not differ between hybrids of the first generation and the backcrosses, but it increases in the second hybrid generation; and (4) pigeons and doves follow Haldane's rule, as found in the other groups studied so far. The similarity between the results of this and previous studies contributes to the growing evidence suggesting that the patterns of the evolution of postzygotic isolation, and the process of speciation in general, are shared among animal groups.     

Alpha-chloralose immobilization of rock doves in Ohio

To improve capture efficacy of rock doves (Columba livia) in nuisance situations, we reevaluated the effectiveness of three dosages (60, 120 and 180 mg/kg) of alpha-chloralose (AC). Responses to immobilization using 180 mg/kg AC also were compared in rock doves deprived of food for 16 hr and not food deprived. Mean (+/- SE) time to first effects (33 +/- 2 min) and mean time to capture (94 +/- 5 min) were significantly less for rock doves receiving 180 mg/kg than for rock doves receiving lower dosages (> or = 53 +/- 3 min and > or = 153 +/- 17 min, respectively). Ten, 10, and eight rock doves immobilized with 60, 120, and 180 mg/kg AC recovered within 24 hr, respectively; all rock doves recovered within 29 hr. Although food-deprived rock doves showed effects of AC immobilization earlier than did rock doves with food, time to capture was similar between these two groups. For capturing rock doves, we recommend treating corn with 3 mg AC/kernel and using 180 mg/kg as the effective dose. This modified formulation and dosage should improve capture success of rock doves substantially and improve the ability to resolve nuisance rock dove problems.     

Heterothermia in pigeons and doves reduces energetic costs

Two patterns of heterothermia were demonstrated for three species of pigeons (Columbidae): Controlled hyperthermia as a physiological strategy of the arid-adapted Australian Diamond Dove and African Namaqua Dove to minimize heat stress when exposed to high temperatures and Torpor as an energy-saving mechanism at low environmental temperatures. This mechanism was most pronounced in the fruit-eating Cloven-feathered Dove (minimal body temperature T_b=25°C, reduction of metabolic rate by 67%). Hence, heterothermia is regarded as a means of adaptation to variable and unpredictable environmental conditions, playing an important role in the ecological radiation of the Columbidae.     

Statewide and local recruitment of mourning doves in Missouri

Intensive harvests have the potential to greatly affect local mourning dove (Zenaida macroura) populations, a popular gamebird and songbird. To evaluate if recruitment was commensurate with harvest, we applied a ratio-based method to estimate local and statewide mourning dove recruitment across 7 public hunting areas in Missouri from 2005 to 2011. We estimated recruitment from preharvest adult sex ratios and harvest age ratios that incorporated various methods to address potential inherent biases (e.g., bias in the adults of unknown sex in preharvest samples, bias in unknown age wings, and local differential vulnerability; DV). Data from 356 radio-marked doves revealed a DV rate, where hatch year doves were, on average 2.7× more likely to be harvested than adult doves. Recruitment estimates for local areas were highly variable and in some cases, biologically unrealistic (e.g., >10 offspring/female), because of small preharvest sample sizes. However, data pooled statewide provided recruitment estimates of 3.1 offspring/female (±0.3 SE) or 4.1 offspring/female (±0.3 SE), assuming samples of unknown sex doves were female biased or male biased, respectively. Although statewide estimates agree with directly observed rates, the sex ratios and differential vulnerability comprising them vary considerably from what has been previously assumed. Whether preharvest sex ratios are biased from trapping methods has 2 important implications; either regional approaches have overestimated recruitment or the number of females in Missouri's population is much less than originally thought. Because each of these scenarios are important to understanding the effects of regional harvest management on Missouri's dove population, they highlight the importance of a better understanding of biases involved in estimating recruitment. © 2012 The Wildlife Society.     

Primary and secondary immune response in animals following spontaneous loss of tolerance

Mice subjected to tolerogenic treatment by sheep red blood cells (SRBC) and cyclophosphamide were immunized at various intervals (from 1 to 8 weeks after treatment) either by a single injection of 5 X 10(8) SRBC or by a double-injection of 1 X 10(6) SRBC. In control mice both immunization methods proved to be equally successful. In the experimental animals the immunological memory formation and/or its realization was destroyed to a greater extent and was restored more slowly than the capacity to the primary response.     

Metabolic and thermal physiology of pigeons and doves

Pigeons and doves (Columbidae) are an interesting group to examine for physiological adaptations to climate and diet because this cosmopolitan family comprises more than 300 species that are mostly granivores, although some are specialized frugivores. We determined allometric and phylogenetic effects on body temperature (T(b)), basal metabolic rate (BMR; J h(-1)), and wet thermal conductance (C(wet); J h(-1) C(-1)), and we examined mass (M) and phylogenetically corrected residuals for further effects of climate, diet, and landmass size (mainland or island). Independent contrasts, correlograms, autoregression, and phylogenetic eigenvector regression (PVR) were used to examine phylogenetically related effects. We found a small but significant phylogenetic pattern for body mass of columbids. For T(b), there was no significant effect of mass or phylogeny. There was a significant effect of climate on T(b) and no significant effects of diet or landmass without mass or phylogenetic correction, but after mass and phylogenetic correction, there were no effects of climate, diet, or landmass. For BMR, there was a strong allometric effect, and residuals were significantly lower for arid and tropical species but not for temperate species, compared to predictions for nonpasserine birds. There was a nearly significant autoregressive phylogenetic relationship for BMR parl0;r=0.44), and the strong allometry of BMR remained for independent contrasts (slope=0.731), autoregressive residuals (0.698), and PVR (0.705). Residuals, from regression of autoregression and PVR residuals of M and BMR, were significantly associated with climate: arid pigeons had a lower BMR residual than tropical and temperate pigeons. PVR residuals were significantly affected by landmass (island columbids had a smaller residual than mainland columbids), but autoregression residuals were not. There was no association of autoregression or PVR residuals with diet. For C(wet), there was a strong allometric effect, and residuals for columbids were significantly higher compared to other birds. There was no significant relationship for C(wet) of columbids to climate, diet, or landmass. There was no significant autoregressive or PVR relationship for C(wet), and the strong allometry remained after phylogenetic analysis by independent contrasts (slope=0.501), autoregression (0.509), and PVR (0.514). Residuals from autoregression and PVR were not significantly correlated with climate, diet, or landmass (mainland/island).