Immunoglobulin allotypes (GM and KM) indicate multiple founding populations of Native Americans: evidence of at least four migrations to the New World.

On the basis of GM and KM typing and language, approximately 28,000 Amerindians were divided into 4 groups of populations: non-Nadene South American (8 groups), non-Nadene North American (7 groups), Nadene (4 groups), and Eskaleuts (6 groups). These groups were compared to four groups of Asian populations. The distribution of GM haplotypes differed significantly among and within these groups as measured by chi-square analysis. Furthermore, as reflected in a maximum linkage cluster analysis, Amerindian populations in general cluster along geographic divisions, with Eskaleuts and Nadenes clustering with the Asian populations and non-Nadene North American and non-Nadene South American populations forming two additional clusters. Based on GM haplotype data and other genetic polymorphisms, the divisions appear to reflect populations that entered the New World at different times. It appears that the South American non-Nadene populations are the oldest, characterized by the haplotypes GM*A G and GM*X G, whereas later North American non-Nadene populations are characterized by high frequencies of GM*A G and low frequencies of GM*X G and GM*A T. In contrast, Eskaleuts appear to have only GM*A G and GM*A T. The Nadene speakers have GM*X G and GM*A T in higher and approximately equal frequencies. Maximum linkage cluster analysis places the Alaskan Athapaskans closest to northwestern Siberian populations and the Eskaleuts closest to the Chukchi, their closest Asian neighbor. These analyses, when combined with other data, suggest that, in the peopling of the New World, at least four separate migrant groups crossed Beringia at various times. It appears likely that the South American non-Nadene entered the New World before 17,000 years B.P. and that the North American non-Nadene entered in the immediate postglacial period, with the Eskaleut and Nadene arriving at a later date.     

GM haplotype diversity of 82 populations over the world suggests a centrifugal model of human migrations

This study investigates the GM genetic relationships of 82 human populations, among which 10 represent original data, within and among the main broad geographic areas of the world. Different approaches are used: multidimensional scaling analysis and test for isolation by distance, to assess the correlation between genetic variation and spatial distributions; analysis of variance, to investigate the genetic structure at different hierarchical levels of population subdivision; genetic similarity map (geographic map distorted by available genetic information), to identify regions of high and low genetic variation; and minimal spanning network, to point out possible migration routes across continental areas. The results show that the GM polymorphism is characterized by one of the highest amounts of genetic variation observed so far among populations of different continents (Fct=0.3915, P < 0.0001). GM diversity can be explained by a model of isolation by distance (IBD) at most continental levels, with a particularly significant fit to IBD for the Middle East and Europe. Five peripheral regions of the world (Europe, west and south sub-Saharan Africa, Southeast Asia, and America) exhibit a low level of genetic diversity both within and among populations. By contrast, East and North African, Southwest Asian, and Northeast Asian populations are highly diverse and interconnected genetically by large genetic distances. Therefore, the observed GM variation can be explained by a "centrifugal model" of modern humans peopling history, involving ancient dispersals across a large intercontinental area spanning from East Africa to Northeast Asia, followed by recent migrations in peripheral geographic regions.     

Spontaneous transfer of ganglioside GM1 from its micelles to lipid vesicles of differing size.

The spontaneous incorporation of II3-N-acetylneuraminosylgangliotetraosylceramide (GM1) from its micelles into phospholipid bilayer vesicles has been investigated to determine whether curvature-induced changes in membrane lipid packing influence ganglioside uptake. Use of conventional liquid chromatography in conjunction with technically-improved molecular sieve gels permits ganglioside micelles to be separated from phospholipid vesicles of different average size including vesicles with diameters smaller than 40 nm and, thus, allows detailed study of native ganglioside GM1 incorporation into model membranes under conditions where complicating processes like fusion are readily detected if present. At 45 degrees C, the spontaneous transfer rate of GM1 from its micelles to small unilamellar vesicles (SUVs) comprised of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) is at least 3-fold faster than that to similar composition large unilamellar vesicles (LUVs) prepared by octyl glucoside dialysis. Careful analysis of ganglioside GM1 distribution among vesicle populations of differing average size reveals that GM1 preferentially incorporates into the smaller vesicles of certain populations. This behavior is observed in SUVs as well as in LUV-SUV mixtures and actually serves as a sensitive indicator for the presence of trace quantities of SUVs in various LUV preparations. Analysis of the results shows that both differences in the diffusional collision frequency between GM1 monomers and either SUVs or LUVs and curvature-induced changes in the interfacial lipid packing in either SUVs or LUVs can dramatically influence spontaneous ganglioside uptake.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immunoglobulin allotypes among Taiwan aborigines: evidence of malarial selection could affect studies of population affinity

The aborigines of Taiwan represent the indigenous inhabitants of the island at the time of the arrival of the Chinese from the mainland. Linguistically, the aboriginal Taiwanese are related to the Malayo-Polynesian-speaking inhabitants of Indonesia and the Philippines. Three tribes occupied lowland areas while six tribes occupied highland areas. Previous studies indicate that genetic markers associated with malaria occur in lowland populations. Though the GM haplotypes are demonstrated to be very useful in the measure of population affinities, the possibility of malarial selection on this locus could affect studies of population affinity. The present work is a case study to see whether a subdivided insular population under a possible selective load will provide divergent clustering analysis depending on the population sampled. Immunoglobulin allotype (GM and KM) profiles were generated on 230 lowland and 407 highland Taiwan Aborigines from the nine tribes. A highly significant difference in GM haplotype distribution was detected between lowland and highland populations (adjusted G = 69.408, 2 df [degrees of freedom], p < 0.00001). There were no significant differences in KM*1 frequency by altitude. The Taiwan Aboriginal GM and KM frequencies were compared to data from Indonesians, Vietnamese, Thai, Malay, Chinese from Taiwan, and Ryukyu Islanders from Okinawa using cluster analysis. The lowland populations plot among the Thai (N, NC) and Malayan Aborigines. In contrast, the highland and total Taiwan Aborigine samples plot with the Indonesian, Vietnamese, and Malayan Negrito samples. Thus, depending on the populations of Taiwan Aborigines used, different conclusions could be reached. The highland population supports the published linguistic ties; however, the lowland population does not support the linguistic relationship with Indonesian populations but is more closely related to Thai and Malays, or reflects a similar selection history.     

Genetic diversity of Annona crassiflora (Annonaceae) in northern Minas Gerais State

Genetic diversity analyses of tropical tree species are relevant to landscape management, plant genetic resource inventory, and biological conservation of threatened species. Annona crassiflora is an endangered fruit tree native to the Cerrado biome that is threatened by reduction of natural populations and fruit extraction. We examined the intra- and interpopulational genetic diversity of this species in the northern region of Minas Gerais State. Seventy-two individuals from four natural populations were genotyped using RAPD markers. We found moderate genetic diversity among populations, with Shannon's I index varying between 0.31 and 0.44, and Nei's genetic diversity (H(E)) for the population set equal to 0.31. AMOVA indicated a greater genetic variation within (77.38%) rather than among populations (22.62%), tending towards isolation by distance (Mantel's r = 0.914; P = 0.089). Nei's genetic identity estimates among populations revealed a hierarchical pattern of genetic similarity of form [(CA1, CA2), MC], [(GM)], corroborating the high genetic differentiation between spatially isolated populations.     

Heterogeneity in the distribution of genetically modified and conventional oilseed rape within fields and seed lots

The implementation of co-existence in the commercialisation of GM crops requires GM and non-GM products to be segregated in production and supply. However, maintaining segregation in oilseed rape will be made difficult by the highly persistent nature of this species. An understanding of its population dynamics is needed to predict persistence and develop potential strategies for control, while to ensure segregation is being achieved, the production of GM oilseed rape must be accompanied by the monitoring of GM levels in crop or seed populations. Heterogeneity in the spatial distribution of oilseed rape has the potential to affect both control and monitoring and, although a universal phenomenon in arable weeds and harvested seed lots, spatial heterogeneity in oilseed rape populations remains to be demonstrated and quantified. Here we investigate the distribution of crop and volunteer populations in a commercial field before and during the cultivation of the first conventional oilseed rape (winter) crop since the cultivation of a GM glufosinate-tolerant oilseed rape crop (spring) three years previously. GM presence was detected by ELISA for the PAT protein in each of three morphologically distinguishable phenotypes: autumn germinating crop-type plants (3% GM), autumn-germinating 'regrowths' (72% GM) and spring germinating 'small-type' plants (17% GM). Statistical models (Poisson log-normal and binomial logit-normal) were used to describe the spatial distribution of these populations at multiple spatial scales in the field and of GM presence in the harvested seed lot. Heterogeneity was a consistent feature in the distribution of GM and conventional oilseed rape. Large trends across the field (50 x 400 m) and seed lot (4 x 1.5 x 1.5 m) were observed in addition to small-scale heterogeneity, less than 20 m in the field and 20 cm in the seed lot. The heterogeneity was greater for the 'regrowth' and 'small' phenotypes, which were likely to be volunteers and included most of the GM plants detected, than for the largely non-GM 'crop' phenotype. The implications of the volunteer heterogeneity for field management and GM-sampling are discussed.     

Modernization,Sexual Risk-Taking,and Gynecological Morbidity among Bolivian Forager-Horticulturalists

Sexual risk-taking and reproductive morbidity are common among rapidly modernizing populations with little material wealth, limited schooling, minimal access to modern contraception and healthcare, and gendered inequalities in resource access that limit female autonomy in cohabiting relationships. Few studies have examined how modernization influences sexual risk-taking and reproductive health early in demographic transition. Tsimane are a natural fertility population of Bolivian forager-farmers; they are not urbanized, reside in small-scale villages, and lack public health infrastructure. We test whether modernization is associated with greater sexual risk-taking, report prevalence of gynecological morbidity (GM), and test whether modernization, sexual risk-taking and parity are associated with greater risk of GM. Data were collected from 2002–2010 using interviews, clinical exams, and laboratory analysis of cervical cells. We find opposing effects of modernization on both sexual risk-taking and risk of GM. Residential proximity to town and Spanish fluency are associated with greater likelihood of men’s infidelity, and with number of lifetime sexual partners for men and women. However, for women, literacy is associated with delayed sexual debut after controlling for town proximity. Fifty-five percent of women present at least one clinical indicator of GM (n = 377); 48% present inflammation of cervical cells, and in 11% the inflammation results from sexually transmitted infection (trichomoniasis). Despite having easier access to modern healthcare, women residing near town experience greater likelihood of cervical inflammation and trichomoniasis relative to women in remote villages; women who are fluent in Spanish are also more likely to present trichomoniasis relative to women with moderate or no fluency. However, literate women experience lower likelihood of trichomoniasis. Parity has no effect on risk of GM. Our results suggest a net increase in risk of reproductive morbidity among rapidly modernizing, resource-stressed populations.     

Heterogeneous selection in subdivided populations

The dynamics of allele frequencies changing under migration and heterogeneous selection in a subdivided population are investigated. Using perturbation techniques, a stationary state is obtained when migration and selection are both small. Heterogeneous selection leads to a positive correlation between values of F-statistics and heterozygosities when these are compared among sets of subdivided populations. This contrasts with a negative value of the correlation obtained under Wright's classical model of homogeneous selection, and with the absence of correlation in the completely neutral situation.Research supported in part by NIH grants GM 28016 and GM 10452 and a grant from the John D. and Catherine T. MacArthur Foundation     

Phylogenetic relationships of human populations in sub-Saharan Africa

This study utilizes the GM/KM immunoglobulin allotype system to elucidate the phylogenetic relationships of sub-Saharan Africans. The importance of understanding the relatedness of these peoples stems from the sub-Saharan region being the possible birthplace of humans. Haplotype distributions were determined for 19 populations and compared using chi-square analysis. Published data of other sub-Saharan Africans and representative populations worldwide were also added for comparison. Genetic distances between populations were calculated based on haplotype frequencies, and genetic relationships were observed through principal components analysis. Data from the GM/KM system showed a genetic homogeneity of the Bantu populations, with some exceptions, supporting the possibility of a common origin of these peoples. The Malagasy appeared as a divergent population, most likely due to Southeast Asian/Austronesian admixture, as indicated by the presence of the GM*AF B haplotype. The Cape Coloured also showed a divergence, with their genetic structures containing Caucasoid and Khoisan contributions. Finally, the Mbuti Pygmies appeared genetically isolated and had the highest frequency of the GM*A B haplotype out of all studied populations.     

Assessing the risk of gene flow from genetically modified trees carrying mitigation transgenes

The increasing use of genetically modified (GM) plants has raised concerns about the escape of transgenes to conventional populations. To counteract possible fitness advantages of GM plants, an advantageous ‘primary transgene’ may be linked to a ‘mitigation’ transgene that is selectively disfavored. A risk related to this technique is the possible break-up of the transgenes. This may lead to the establishment of genotypes that only express the primary transgenic trait and are therefore selectively favored over both conventional and GM genotypes. We study here how the establishment of break-up genotypes in tree populations depends on life history, pollen dispersal kernels, and the linkage between transgenes. To this end, we model the dynamics of an initially homozygous GM population and a conventional population growing next to each other. The simulations are based on a spatially explicit simulation model for population-genotype dynamics. Pollen and seed dispersal are described by fat-tailed dispersal kernels. Break-up of transgenes is due subsequent crossing of GM and conventional genotypes. The spatial pattern of pollen and seed dispersal causes break-up and establishment of new invasive genotypes to occur mostly in the conventional population. The amount of individuals of these genotypes established in the conventional population depends on the interaction between life-history traits, pollen dispersal distances and the linkage of the transgenes. Thus, risk assessment of transgene break-up requires information on the genetics, local dynamics, and dispersal of GM and conventional varieties. The approach presented here provides a tool for combining these different sources of information, and it contributes to the formulation of general rules for the management of GM tree populations.     

Characterization of mononuclear phagocytes in schistosomal egg granulomas of athymic mice

Macrophages from schistosomal egg granulomas of athymic mice (nu/nu GM) and their euthymic littermates (nu/+ GM) were analyzed phenotypically for the expression of antigens encoded by the I-A subregion of the major histocompatibility complex and for their ability to perform as antigen-presenting cells. Only 11 to 15% of nu/nu GM expressed I-A antigens as compared to 61.5 to 75% of nu/+ GM. Although both populations of cells appeared to be equally effective as antigen-presenting cells appropriately sensitized lymphocytes in the presence of specific antigens--soluble schistosomal egg antigen (SEA) and human gamma-globulin (HGG)--only nu/nu GM, but not nu/+ GM, were found to stimulate I-A-restricted proliferation of schistosome-sensitized T cell populations in the absence of SEA added in vitro. Furthermore, nu/nu GM but not nu/+ GM were shown to exhibit significant proliferative capacity in vitro, but this phenomenon could not account for the observed difference in SEA-independent T cell stimulation. Finally, culture supernatants from nu/nu GM displayed significant thymocyte-stimulating activity, consistent with interleukin 1, which was not observed in nu/+ GM. These findings point to significant differences between nu/nu GM and nu/+ GM, which may be part of an adaptive mechanism of granulomatous reactivity in the absence of a competent T cell system.     

GM polymorphism and the evolutionary history of modern humans

Present human populations show a complex network of genetic relationships, which reflects mainly their unique origin and their migration and isolation history since the recent creation of modern man. The scrutiny of their genetic characteristics, according to GM polymorphism, shows that the continuity of the genetic variation between populations from neighbouring continents, assured by intermediate world part populations, is against any attempt to divide present human populations into major groups. GM polymorphism analysis also shows three remarkable levels of genetic differentiation, which would have appeared, respectively, within populations of sub-Saharan Africa, Europe and East Asia. The first small groups of people that split from the common ancestral population gave the sub-Saharan Africans. On the other hand, Asians diverged mainly from Europeans and Near East populations during a later period. The confrontation between the phylogeny and the frequency distribution of GM haplotypes shows that the ancestral population of actual South-Arabia people could be a candidate for a common ancestral population. The first major expansions of modern humans were proposed in a hypothetical scenario, which will open a new track in the research of our geographic origin.     

Crop seed spillage along roads: a factor of uncertainty in the containment of GMO

Feral populations of crop species along roadsides contribute to the uncertainty regarding the containment of genetically modified (GM) crops, as the feral populations could promote the persistence of transgenes outside of cultivated fields. Roadside populations of several common crop species are known to occur far from arable fields, and the dispersal pathways that promote their recruitment in road verges are unclear. Human-aided dispersal, in particular adhesive dispersal by vehicles, has been suggested as a possible vector, but this has not yet been proven experimentally. We sampled the seed rain from vehicles inside two motorway tunnels in an urban environment to reveal the contribution of crop species to seeds unintentionally dispersed by traffic beyond agricultural production areas. Three species of arable crops, wheat Triticum aestivum , rye Secale cereale and oilseed rape Brassica napus , were among the most frequent species deposited by vehicles inside the motorway tunnels. Each of the three species was clearly more predominant in one direction of traffic. While seeds of Triticum aestivum and Secale cereale were primarily transported into the city, Brassica napus was significantly more abundant in samples from lanes leading out of the city. Seed sources in the local surroundings of the tunnels were virtually nonexistent, and the high magnitude of seed deposition combined with high seed weights suggests a dispersal mechanism different from other species in the sample, at least for Triticum aestivum and Secale cereale . This provides evidence that spillage during transport is a major driver for long-distance dispersal of crops. Our results suggest that seed dispersal by vehicles is the major driver in the recruitment of roadside populations of arable crops, providing a possible escape route for GM crops. Risk management should thus aim at curbing transport losses of GM crops.     

Extensive variability in the gut microbiome of a highly‐specialized and critically endangered lemur species across sites

Deforestation continues to jeopardize Malagasy primates as viable habitats become smaller, more fragmented, and more disturbed. This deforestation can lead to changes in diet, microhabitat, and gene flow between populations of endangered species, and it remains unclear how these changes may affect gut microbiome (GM) characteristics. The black‐and‐white ruffed lemur (Varecia variegata), which is among Madagascar's most threatened lemur species, provides a critical model for understanding the relationships between historical and on‐going deforestation (habitat disturbance), feeding ecology, and GM composition and diversity. We studied four populations inhabiting two rainforests (relatively pristine vs. highly disturbed) in southeastern Madagascar. We conducted full‐day focal animal behavioral follows and collected fecal samples opportunistically across a three‐month period. Our results indicate that lemurs inhabiting sites characterized by habitat disturbance and low dietary diversity exhibited reduced gut microbial alpha diversity. We also show that these same factors were associated with high community dissimilarity using weighted and unweighted UniFrac metrics. Finally, an indicator species analysis showed that the most pristine site was characterized by an abundance of methanogenic archaea. While it is impossible to disentangle the relative contributions of each confounding variable presented by our sampling design, these results provide crucial information about GM variability, thereby underscoring the importance of monitoring endangered species at the population‐level.     

Immunoglobulin allotypes in several North American Eskimo populations

Genetic data consisting of immunoglobulin testing (GM and KM) from 631 Eskimos from 5 populations are reported. These populations are Savoonga, Gambell (St. Lawrence Island), Wales, King Island, and Mckenzie Delta, Baffin Island. The GM and KM haplotypes are analyzed and compared to those occurring in Greenland, Canadian, Alaskan, and Siberian Eskimos and to other Siberian indigenous populations. These analyses suggest that during the peopling of the New World, four separate migrant groups crossed Beringia at various times.     

Immunoglobulin (GM and KM) allotypes in the Sikh population of India

The populations of India are genetically diverse, both within and between geographic regions; immunoglobulin (GM) allotypes provide important information on genetic differences between populations, since the frequencies of combinations of allotypes (termed "haplotypes") vary dramatically among ethnic groups. As part of a project to assess genetic diversity among defined Indian populations, we have examined eight GM allotypes in a sample of 101 unrelated Sikhs who have migrated to Toronto, Canada: Glm(1, 2, 3, 17) and G3m (5, 15, 16, 21). Sikhs are a religious group that arose in the Punjab about 1500 A.D.; most of the original converts are believed to have been middle to upper-middle caste Hindus. Gm allotyping showed that six Gm haplotypes occurred at polymorphic frequencies (greater than 0.01) in Sikhs: Gm3;5, Gm1,17;21, Gm1,2,17;21, Gm1,17;5, Gm1,17;15,16, and Gm1,3;5. These haplotypes have all been previously reported in Indian populations. The frequencies of the first four haplotypes resembled the published frequencies for lower-caste Hindus of NW India more than upper-caste Hindus. However, the last two haplotypes have been found only in upper-caste Hindus. The frequency of one of these, Gm1,17;15,16 was higher in Sikhs (0.09) than has been reported in any Indian population with the exception of Parsis (who are descended from Iranians). We speculate that the high frequency of this haplotype may have been characteristic of some of the Hindu castes in the Punjab from which Sikhs are descended.     

Genetic position of Andalusians from Huelva in relation to other European and North African populations: a study based on GM and KM allotypes

An understanding of population relationships in the Mediterranean region is crucial to the reconstruction of recent human evolution. Andalusia, the most southern region of Spain, has been continuously and densely occupied since ancient times and has a rich history of contacts with many different Mediterranean populations. Thus, to understand the Mediterranean peopling process, investigators should analyze the population relationships between the Iberian peninsula and northern Africa based on an assessment of genetic diversity that takes Andalusia into consideration. The aim of this study was to address the extent of genetic variation in the Iberian peninsula between its geographic extremes (Huelva and the Basque area) and to explain the intensity of the phylogenetic relationships between Andalusians and other neighboring populations, such as those from North Africa. We present, for the first time, results on allotype markers (GM and KM) of human immunoglobulins in the Andalusian population from Huelva. The most frequent GM haplotypes in Andalusia correspond to those that are also the most common in Europe. A sub-Saharan haplotype was found at a relatively high frequency compared to other Iberian samples, and a North Asian marker did not reach polymorphic frequencies in the study sample. A hierarchical cluster analysis based on the first two principal components (94.1% of the total genetic variance) revealed an interesting geographic structure for the 49 populations selected from the literature. The Huelva sample showed a central position in the multivariate space--despite being geographically located at one of the extremes of the Mediterranean basin--and clustered with most Western European populations. Western Europe and Eastern Europe (the latter group paradoxically including Italy and the major islands of the western Mediterranean) were differentiated. North African populations were grouped in two clusters that did not separate either Arabs and Berbers or their present-day countries. Analysis of immunoglobulin allotype markers shows that gene flow among human populations should generally be interpreted in terms of complex patterns, with the observed frequencies being the consequence of the entire genetic and demographic history of the population. Single historical events rarely determine gene frequencies in large human populations. Analysis of the GM system has shown that the Andalusian population from Huelva, as a result of its complex history, is not simply an outstanding part of the Mediterranean world but rather the genetic center of gravity of that world.     

The genetic position of the autochthonous subpopulation of Northern Navarre (Spain) in relation to other basque subpopulations. A study based on GM and KM immunoglobulin allotypes

GM and KM immunoglobulin (Ig) allotypes were tested in 118 autochthonous Basques from northern Navarre. The results are compared to those obtained for the same genetic markers in 6 other Basque subpopulations, 3 from Spain (Guipúzcoa, Vizcaya, and Alava) and 3 from France: Macaye, Saint-Jean Pied de Port, and Mauleon. The northern Navarrese appear genetically closer to the Alava and Saint-Jean Pied de Port subpopulations. The Basques present 3 GM haplotypes that are uncommon in Caucasian populations, suggesting that they have not been completely isolated either from Asian or African populations. The GM*1,17 23' 10,11,13,15,16 north Asian haplotype was probably the first to be introduced into the Basque area. The GM*1,17 23' 5* haplotype, considered an African genetic marker although also detected in Central Asia, would have reached the Iberian Peninsula through consecutive historic migrations from North Africa. The rare haplotype GM*1,17 23 21,28 results probably from a genetic recombination or crossing-over between the 2 common haplotypes GM*1, 17 23' 21,28 and GM*3 23 5*. It is also found with a low frequency in other neighboring regions and countries; but the possibility of its having been introduced through the main passage connecting western France and Spain during the Roman Empire and Middle Ages cannot be ruled out.     

Cytokine expanded myeloid precursors function as regulatory antigen-presenting cells and promote tolerance through IL-10-producing regulatory T cells

The initiation of graft-vs-host disease (GVHD) after stem cell transplantation is dependent on direct Ag presentation by host APCs, whereas the effect of donor APC populations is unclear. We studied the role of indirect Ag presentation in allogenic T cell responses by adding populations of cytokine-expanded donor APC to hemopoietic grafts that would otherwise induce lethal GVHD. Progenipoietin-1 (a synthetic G-CSF/Flt-3 ligand molecule) and G-CSF expanded myeloid dendritic cells (DC), plasmacytoid DC, and a novel granulocyte-monocyte precursor population (GM) that differentiate into class II+,CD80/CD86+,CD40- APC during GVHD. Whereas addition of plasmacytoid and myeloid donor DC augmented GVHD, GM cells promoted transplant tolerance by MHC class II-restricted generation of IL-10-secreting, Ag-specific regulatory T cells. Importantly, although GM cells abrogated GVHD, graft-vs-leukemia effects were preserved. Thus, a population of cytokine-expanded GM precursors function as regulatory APCs, suggesting that G-CSF derivatives may have application in disorders characterized by a loss of self-tolerance.