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In contrast, anti-CD137 agonistic mAbs can suppress T-dependent humoral immunity and reverse the course of established autoimmune disease. These results have provided a rationale for assessing the therapeutic potential of CD137 ligands in human clinical trials. In this study, we report that a single 200-\u03bcg injection of anti-CD137 given to otherwise naive BALB\/c or C57BL\/6 mice led to the development of a series of immunological anomalies. These included splenomegaly, lymphadenopathy, hepatomegaly, multifocal hepatitis, anemia, altered trafficking of B cells and CD8 T cells, loss of NK cells, and a 10-fold increase in bone marrow (BM) cells bearing the phenotype of hemopoietic stem cells. These events were dependent on CD8 T cells, TNF-\u03b1, IFN-\u03b3, and type I IFNs. BM cells up-regulated Fas, and there was a significant increase in the number of CD8+ T cells that correlated with a loss of CD19+ and Ab-secreting cells in the BM. TCR V\u03b1\u03b2 usage was random and polyclonal among liver-infiltrating CD8 T cells, and multifocal CD8+ T cell infiltrates were resolved upon termination of anti-CD137 treatment. Anti-CD137-treated mice developed lymphopenia, thrombocytopenia, and anemia, and had lowered levels of hemoglobin and increased numbers of reticulocytes.<\/jats:p>","DOI":"10.4049\/jimmunol.178.7.4194","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T22:53:35Z","timestamp":1397861615000},"page":"4194-4213","source":"Crossref","is-referenced-by-count":150,"title":["Cytokine-Mediated Disruption of Lymphocyte Trafficking, Hemopoiesis, and Induction of Lymphopenia, Anemia, and Thrombocytopenia in Anti-CD137-Treated Mice"],"prefix":"10.1093","volume":"178","author":[{"given":"Liguo","family":"Niu","sequence":"first","affiliation":[{"name":"Emory Vaccine Research Center, Emory University School of Medicine , Atlanta, GA 30329"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Strahotin","sequence":"additional","affiliation":[{"name":"Emory Vaccine Research Center, Emory University School of Medicine , Atlanta, GA 30329"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Becker","family":"Hewes","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Emory University School of Medicine , Atlanta, GA 30329"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benyue","family":"Zhang","sequence":"additional","affiliation":[{"name":"Emory Vaccine Research Center, Emory University School of Medicine , Atlanta, GA 30329"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Emory Vaccine Research Center, Emory University School of Medicine , Atlanta, GA 30329"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Archer","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Emory University School of Medicine , Atlanta, GA 30329"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trent","family":"Spencer","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Emory University School of Medicine , Atlanta, GA 30329"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirck","family":"Dillehay","sequence":"additional","affiliation":[{"name":"Department of Animal Resources, Emory University School of Medicine , Atlanta, GA 30329"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byoung","family":"Kwon","sequence":"additional","affiliation":[{"name":"The Immunomodulation Research Center, University of Ulsan , Ulsan ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lieping","family":"Chen","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine, Department of Dermatology , Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony T","family":"Vella","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Connecticut Health Center , Farmington, CT 06030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert S","family":"Mittler","sequence":"additional","affiliation":[{"name":"Emory Vaccine Research Center, Emory University School of Medicine , Atlanta, GA 30329"},{"name":"Department of Surgery, Emory University School of Medicine , Atlanta, GA 30329"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2007,4,1]]},"reference":[{"key":"2025032802441771200_R1","first-page":"23","volume-title":"Annu. 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