Significant mobilization of both conventional and regulatory T cells with AMD3100

被引:63
作者
Kean, Leslie S. [1 ,2 ]
Sen, Sharon [1 ]
Onabajo, Olusegun [3 ]
Singh, Karnail [2 ]
Robertson, Jennifer [2 ]
Stempora, Linda [2 ]
Bonifacino, Aylin C. [4 ]
Metzger, Mark E. [4 ]
Promislow, Daniel E. L. [5 ]
Mattapallil, Joseph J. [3 ]
Donahue, Robert E. [4 ]
机构
[1] Childrens Healthcare Atlanta, Dept Pediat, Atlanta, GA 30322 USA
[2] Emory Univ, Sch Med, Emory Transplant Ctr, Dept Surg, Atlanta, GA 30322 USA
[3] Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA
[4] NHLBI, Hematol Branch, NIH, Rockville, MD USA
[5] Univ Georgia, Dept Genet, Athens, GA 30602 USA
关键词
COLONY-STIMULATING FACTOR; VERSUS-HOST-DISEASE; BONE-MARROW; HEMATOPOIETIC STEM; CXCR4; ANTAGONIST; PROGENITOR CELLS; RHESUS MACAQUES; HEMATOLOGIC MALIGNANCIES; COSTIMULATION BLOCKADE; NONHUMAN-PRIMATES;
D O I
10.1182/blood-2011-06-359331
中图分类号
R5 [内科学];
学科分类号
100201 [内科学];
摘要
In this study, we used the rhesus macaque model to determine the impact that AMD3100 has on lymphocyte mobilization, both alone and in combination with G-CSF. Our results indicate that, unlike G-CSF, AMD3100 substantially mobilizes both B and T lymphocytes into the peripheral blood. This led to significant increases in the peripheral blood content of both effector and regulatory T-cell populations, which translated into greater accumulation of these cells in the resulting leukapheresis products. Notably, CD4(+)/CD25(high)/CD127(low)/FoxP3(+) Tregs were efficiently mobilized with AMD3100-containing regimens, with as much as a 4.0-fold enrichment in the leukapheresis product compared with G-CSF alone. CD8(+) T cells were mobilized to a greater extent than CD4(+) T cells, with accumulation of 3.7 +/- 0.4-fold more total CD8+ T cells and 6.2 +/- 0.4-fold more CD8(+) effector memory T cells in the leukapheresis product compared with G-CSF alone. Given that effector memory T-cell sub-populations may mediate less GVHD compared with other effector T-cell populations and that Tregs are protective against GVHD, our results indicate that AMD3100 may mobilize a GVHD-protective T-cell repertoire, which would be of benefit in allogeneic hematopoietic stem cell transplantation. (Blood. 2011;118(25):6580-6590)
引用
收藏
页码:6580 / 6590
页数:11
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