ChimerismPub Date : 2011-04-01DOI: 10.4161/chim.2.2.16783
J Scott Bryson, J Anthony Brandon, C Darrell Jennings, Alan M Kaplan
{"title":"A gut feeling about murine syngeneic GVHD.","authors":"J Scott Bryson, J Anthony Brandon, C Darrell Jennings, Alan M Kaplan","doi":"10.4161/chim.2.2.16783","DOIUrl":"https://doi.org/10.4161/chim.2.2.16783","url":null,"abstract":"Murine syngeneic graft-versus-host disease (SGVHD) results in chronic colon and liver inflammation following syngeneic bone marrow transplantation (BMT) and treatment with the calcineurin inhibitor, cyclosporine A (CsA). SGVHD was initially thought to arise as a result of an autoreactive immune response, but more recently it has been shown that enhanced antimicrobial responses develop in SGVHD mice. Consequently, we performed studies to analyze the role of the microbiota in the development of murine SGVHD. Treatment with broad-spectrum antibiotics eliminated disease-associated inflammatory immune responses and pathology, linking the role of the microbiota and microbial-specific immunity to the development of murine SGVHD. In a broader context, these results bring into question the role that anti-microbial immune responses play in post-transplant immune pathologies that develop following allogeneic stem cell transplantation and use of calcineurin inhibitors.","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"2 2","pages":"58-60"},"PeriodicalIF":0.0,"publicationDate":"2011-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/chim.2.2.16783","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30137777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ChimerismPub Date : 2011-04-01DOI: 10.4161/chim.2.2.16287
Amar Nijagal, Marta Wegorzewska, Tom Le, Qizhi Tang, Tippi C Mackenzie
{"title":"The maternal immune response inhibits the success of in utero hematopoietic cell transplantation.","authors":"Amar Nijagal, Marta Wegorzewska, Tom Le, Qizhi Tang, Tippi C Mackenzie","doi":"10.4161/chim.2.2.16287","DOIUrl":"https://doi.org/10.4161/chim.2.2.16287","url":null,"abstract":"<p><p>In utero hematopoietic cell transplantation (IUHCTx) is a promising strategy for the treatment of congenital stem cell disorders. Despite the purported immaturity of the fetal immune system, the clinical success of this strategy has been limited by poor engraftment of transplanted cells. The fetal host immune system is thought to be the major barrier to achieving successful IUHCTx. Since the fetal immune system is immature, however, we hypothesized that the maternal immune response may instead pose the true barrier to IUHCTx. We have demonstrated that maternal T cells traffic into the fetus after allogeneic in utero transplantation and that these lymphocytes play a critical role in limiting engraftment. Furthermore, we have shown that MHC matching the donor cells to the mother improves engraftment in the unmatched fetus. These results help renew interest in using the fetal environment to treat patients with congenital stem cell disorders. </p>","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"2 2","pages":"55-7"},"PeriodicalIF":0.0,"publicationDate":"2011-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/chim.2.2.16287","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30137776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ChimerismPub Date : 2011-04-01DOI: 10.4161/chim.2.2.16446
Jesús M López-Guisa, Rebecca Howsmon, Andrew Munro, Kendall M Blair, Edward Fisher, Heidi Hermes, Richard Zager, Anne M Stevens
{"title":"Chimeric maternal cells in offspring do not respond to renal injury, inflammatory or repair signals.","authors":"Jesús M López-Guisa, Rebecca Howsmon, Andrew Munro, Kendall M Blair, Edward Fisher, Heidi Hermes, Richard Zager, Anne M Stevens","doi":"10.4161/chim.2.2.16446","DOIUrl":"https://doi.org/10.4161/chim.2.2.16446","url":null,"abstract":"<p><p>Maternal microchimerism (MMc) can persist for years in a child, and has been implicated in the pathogenesis of chronic inflammatory autoimmune diseases. Chimeric cells may either contribute to disease by acting as immune targets or expand in response to signals of injury, inflammation or repair. We investigated the role of maternal cells in tissue injury in the absence of autoimmunity by quantifying MMc by quantitative PCR in acute and chronic models of renal injury: (1) reversible acute renal injury, inflammation and regeneration induced by rhabdomyolysis and (2) chronic injury leading to fibrosis after unilateral ureteral obstruction. We found that MMc is common in the mouse kidney. In mice congenic with their mothers neither acute nor chronic renal injury with fibrosis influenced the levels or prevalence of MMc. Maternal cells expressing MHC antigens not shared by offspring (H2(b/d)) were detected at lower levels in all groups of homozygous H2(b/b) or H2(d/d) offspring, with or without renal injury, suggesting that partial tolerance to low levels of alloantigens may regulate the homeostatic levels of maternal cells within tissues. Maternal cells homozygous for H2(b) were lost in H2(b/d) offspring only after acute renal failure, suggesting that an inflammatory stimulus led to loss of tolerance to homozygous maternal cells. The study suggests that elevated MMc previously found in association with human autoimmune diseases may not be a response to non-specific injury or inflammatory signals, but rather a primary event integral to the pathogenesis of autoimmunity. </p>","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"2 2","pages":"42-9"},"PeriodicalIF":0.0,"publicationDate":"2011-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/chim.2.2.16446","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30137774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ChimerismPub Date : 2011-04-01DOI: 10.4161/chim.2.2.16556
David L Suskind, Denice Kong, Anne Stevens, Ghassan Wahbeh, Denise Christie, Lee-Ann Baxter-Lowe, Marcus O Muench
{"title":"Maternal microchimerism in pediatric inflammatory bowel disease.","authors":"David L Suskind, Denice Kong, Anne Stevens, Ghassan Wahbeh, Denise Christie, Lee-Ann Baxter-Lowe, Marcus O Muench","doi":"10.4161/chim.2.2.16556","DOIUrl":"https://doi.org/10.4161/chim.2.2.16556","url":null,"abstract":"<p><strong>Unlabelled: </strong>Inflammatory bowel disease (IBD) shares many immunologic and clinical characteristics with graft versus host disease caused by allogeneic T lymphocytes after hematopoietic cell transplantation. Since maternal cells are known to enter the fetal circulation in a high proportion of pregnancies, we hypothesized that maternal engraftment in the fetus results in immune sequelae that can lead to IBD.</p><p><strong>Method: </strong>The presence and extent of maternal microchimerism in tissues and blood samples from patients with Crohn's, Ulcerative colitis (UC), and control groups were determined using kinetic Polymerase Chain Reaction (kPCR) to detect maternal- and patient-specific HLA types. In addition, fluorescent in situ hybridization (FISH) was employed to detect maternal cells in biopsies from patients with IBD.</p><p><strong>Results: </strong>Using kPCR, maternal microchimerism was observed in 9 of the 16 (56%) patients with IBD and 6 out of 15 of the control group (40%) (P=NS). Five of 10 Crohn's patients had evidence of maternal microchimerism (50%) (P=NS). Four of six UC patients had evidence of maternal microchimerism in gut tissues (67%) (P=NS). There was no correlation between maternal michrochimerism and disease activity, disease location or granulomas in patients with IBD. Using FISH, five male Crohn's and five male UC patient's intestinal biopsies were analyzed for maternal microchimerism. No maternal cells were identified.</p><p><strong>Conclusion: </strong>There is nothing in the data to suggest that patients with IBD differ from disease controls in their frequency of maternal microchimerism in either blood or gut mucosal tissues. These data suggest that maternal microchimerism in blood and biopsies is a relatively common phenomenon that has neither positive nor negative impact on IBD.</p>","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"2 2","pages":"50-4"},"PeriodicalIF":0.0,"publicationDate":"2011-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/chim.2.2.16556","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30137775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ChimerismPub Date : 2011-04-01DOI: 10.4161/chim.2.2.16329
Jeff E Mold, Joseph M McCune
{"title":"At the crossroads between tolerance and aggression: Revisiting the \"layered immune system\" hypothesis.","authors":"Jeff E Mold, Joseph M McCune","doi":"10.4161/chim.2.2.16329","DOIUrl":"10.4161/chim.2.2.16329","url":null,"abstract":"<p><p>\"We do not grow absolutely, chronologically. We grow sometimes in one dimension, and not in another; unevenly. We grow partially. We are relative. We are mature in one realm, childish in another. The past, present and future mingle and pull us backward, forward, or fix us in the present. We are made up of layers, cells, constellations.\"-Anaïs NinIt has long been recognized that the developing immune system exhibits certain peculiarities when compared to the adult immune system. Nonetheless, many still regard the fetal immune system as simply being an immature version of the adult immune system. Here we discuss historical evidence as well as recent findings, which suggest that the human immune system may develop in distinct layers with specific functions at different stages of development. </p>","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"2 2","pages":"35-41"},"PeriodicalIF":0.0,"publicationDate":"2011-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3166482/pdf/chim0202_0035.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30137773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ChimerismPub Date : 2011-01-01DOI: 10.4161/chim.2.1.14726
Donát Alpár
{"title":"Recurrent disease or donor cell leukemia?: Brain teaser after allogeneic bone marrow transplantation.","authors":"Donát Alpár","doi":"10.4161/chim.2.1.14726","DOIUrl":"https://doi.org/10.4161/chim.2.1.14726","url":null,"abstract":"<p><p>Allogeneic bone marrow transplantation (allo-BMT) is the treatment of choice for many patients with poor prognosis or refractory leukemia. Chimerism and residual tumor load after allo-BMT are widely monitored to detect impending graft rejection and the early phase of relapse. In most cases, the malignant cell population during post-transplant relapse contains host-derived cells, but the leukemic clone can rarely be of donor-cell origin. Various genetic tests with different strategies, targets and sensitivities are available for donor-host discrimination. However, changes in the genomic material of the dominant host cell population as a result of clonal evolution and/or clonal selection can hamper the correct identification of the origin of aberrant cells after allo-BMT, thus confounding the assessment of the chimeric state. Consequently, a good knowledge of the techniques applied in clinical practice and careful interpretation of their results are essential. A lack of host-specific markers at the time of clinical relapse is not adequate for verifying the presence of donor cell leukemia, and unequivocal demonstration of donor-specific markers is also required. </p>","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"2 1","pages":"19-20"},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084952/pdf/chim0201_0019.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29861968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ChimerismPub Date : 2011-01-01DOI: 10.4161/chim.2.1.15083
Govindarajan Thangavelu, Colin C Anderson
{"title":"Divide and conquer: Blocking graft versus host but not graft versus leukemia T cells with agonist BTLA co-inhibitory signals.","authors":"Govindarajan Thangavelu, Colin C Anderson","doi":"10.4161/chim.2.1.15083","DOIUrl":"https://doi.org/10.4161/chim.2.1.15083","url":null,"abstract":"<p><p>One of the main objectives in allogeneic hematopoietic stem cell transplantation (aHSCT) research is the prevention of graft versus host disease (GVHD) while maintaining the graft versus leukemia/lymphoma (GVL) effect. Whether these two responses generated by donor T cells can be sufficiently separated and controlled remains controversial. While various approaches have been tested to achieve this goal, success has been relatively limited. Lymphocyte responses are negatively regulated by a series of receptors that function along with antigen receptors to deliver co-inhibitory signals. B and T lymphocyte associated (BTLA) is a novel co-inhibitory molecule expressed by activated T cells, B cells and other immune cells. A study by Albring et al. has now shown in a murine model that a single injection of agonistic anti-BTLA monoclonal antibody can inhibit GVHD long-term while maintaining GVL responses and immunity to infection. These studies suggest that future development of biologics to harness the function of co-inhibitory signals will be an important approach in the prevention of autoimmunity and GVHD and in protocols to achieve transplantation tolerance. </p>","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"2 1","pages":"29-32"},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084956/pdf/chim0201_0029.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29861972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ChimerismPub Date : 2011-01-01DOI: 10.4161/chim.2.1.14725
Baruch Rinkevich
{"title":"Quo vadis chimerism?","authors":"Baruch Rinkevich","doi":"10.4161/chim.2.1.14725","DOIUrl":"https://doi.org/10.4161/chim.2.1.14725","url":null,"abstract":"<p><p>Although immunity in multicellular organisms is efficient in dealing with alien agents, it may fail for allogeneic chimerism. Natural chimerism is widely documented in nature, distributed in at least ten phyla of protists, invertebrates and plants, vertebrates and mammals, including humans; it is an important ecological/evolutionary tool manipulating metazoans' life history portraits. Instead of purging allogeneic nascent selfish cells, a 'double edged sword' chimerism emerges, displaying environmental dictated costs and benefits for the genotypes involved. Benefits include the development of synergistic complementation, the increase of genetic variability, the assurance of mate location, improved size-dependent ecological qualities (growth rates, reproduction, survivorship, competition, environmental tolerance) and more. Costs include the threat of somatic and germ cell parasitism, developmental instability, death, diseases, autoimmunity, sexual sterility and organ malformations, which develop as well in mammalian natural chimerism, including humans. Because of its importance, medical sciences should study and harness natural chimerism properties for clinical purposes. </p>","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"2 1","pages":"1-5"},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084948/pdf/chim0201_0001.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29861453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ChimerismPub Date : 2011-01-01DOI: 10.4161/chim.2.1.15424
Katherine A Guthrie, Hilary S Gammill, Margaret M Madeleine, Carin E Dugowson, J Lee Nelson
{"title":"Parity and HLA alleles in risk of rheumatoid arthritis.","authors":"Katherine A Guthrie, Hilary S Gammill, Margaret M Madeleine, Carin E Dugowson, J Lee Nelson","doi":"10.4161/chim.2.1.15424","DOIUrl":"https://doi.org/10.4161/chim.2.1.15424","url":null,"abstract":"<p><p>Specific HLA II alleles are associated with rheumatoid arthritis (RA) risk and others with protection. Risk-associated alleles encode similar amino acid sequences from 70 through 74 of HLA-DRβ1 (QKRAA, QRRAA, RRRAA), referred to as the \"shared epitope\" (SE) and protective alleles encode DERAA at the same location. Fetal-maternal cell exchange results in long-term microchimerism i.e. harboring small numbers of genetically disparate cells. Women with RA who lack the SE were recently found to harbor microchimerism with the SE more often than healthy women. This finding raises the question whether microchimerism with DERAA confers benefit against RA and is underscored by the observation that overall parity reduces RA risk. While there is currently no test for microchimerism with DERAA, we conducted studies to ask whether parity benefits women at risk for RA, either because they have the SE or lack the protective DERAA sequence. HLA genotyping was conducted for 310 RA and 571 healthy women. Parity was associated with reduced RA risk in women aged <45 years (RR 0.53, 95% CI 0.34-0.82) and further analyses examined this group. RA risk reduction with parity was greater among women with the SE than SE-negative women (RR 0.42, 95%CI 0.22-0.79 vs. RR 0.79, 0.38-1.64). Among women without DERAA, RA risk was significantly reduced with parity (RR 0.44, 95% CI 0.26-0.74) but not among DERAA-positive women (RR 0.95 95% CI 0.34-2.65). In summary, results indicate the effect of parity varied according to a woman's HLA-genotype, and women at increased risk of RA benefited most. </p>","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"2 1","pages":"11-5"},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084950/pdf/chim0201_0011.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29861966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Fetomaternal microchimerism: Some answers and many new questions.","authors":"Kian Hwa Tan, Xiao Xia Zeng, Piriya Sasajala, Ailing Yeo, Gerald Udolph","doi":"10.4161/chim.2.1.14692","DOIUrl":"https://doi.org/10.4161/chim.2.1.14692","url":null,"abstract":"<p><p>The transfer of fetal cells into mothers during pregnancy and their organ specific integration is a well recognized phenomenon in placental vertebrates. Recently, it has been reported that some fetal cells found in the mothers have progenitor cell-like features such as multilineage differentiation potential and as a consequence they were termed pregnancy associated progenitor cells (PAPC). The multilineage differentiation potential suggested some level of cellular plasticity, which these cells share with other stem or progenitor cells. In this context, we have shown that PAPCs indeed express neural stem cell and markers for developing neurons in the brain and that PAPCs morphologically mature into neurons over time. The stem/progenitor properties of PAPCs raises the hope that they might be valuable for studying the functional integration of foreign cells into preexisting tissues and organs, for example in cellular therapies. The functional integration of transplanted cells and their connectivity to the host circuitry is still a major bottleneck in cellular therapies particularly for the brain. The animal models of fetomaternal microchimerism might provide valuable insights into the mechanism how cells survive, migrate, integrate and differentiate in a foreign environment of a host. This review discusses some of the recent findings in the field of fetomaternal microchimerism. It also tries to identify some major gaps of knowledge and raises some questions resulting from the recent advances. Studying fetomaternal microchimerism and the properties of PAPCs in greater detail might pave the way to advance cell based regenerative medicine as well as transplantation medicine. </p>","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"2 1","pages":"16-8"},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084951/pdf/chim0201_0016.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29861967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}