Interleukin-7 improves CD4 T-cell reconstitution after autologous CD34 cell transplantation in monkeys

被引:67
作者
Storek, J
Gillespy, T
Lu, HL
Joseph, A
Dawson, MA
Gough, M
Morris, J
Hackman, RC
Horn, PA
Sale, GE
Andrews, RG
Maloney, DG
Kiem, HP
机构
[1] FHCRC, Seattle, WA USA
[2] Univ Washington, Seattle, WA 98195 USA
关键词
D O I
10.1182/blood-2002-08-2671
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
In mice, interleukin-7 (IL-7) hastens T-cell reconstitution and might cause autoimmune diseases, lymphoma, and osteoporosis. We assessed the effect of IL-7 on T-cell reconstitution and toxicity in baboons that underwent total body irradiation followed by autologous transplantation of marrow CD34 cells. Three baboons received placebo and 3 baboons received recombinant human IL-7 (rhIL-7, 75 mug/kg twice a day subcutaneously) between 6 and 10 weeks after transplantation. The mean increase in blood absolute CD4 T-cell counts was 0.9-fold in the placebo-treated animals versus 9.0-fold in those treated with IL-7 (P = .02). The increase observed in the IL-7-treated animals appeared attributable to peripheral expansion rather than de novo generation. The IL-7-treated animals had greater mean increases in the volumes of the spleen (2.0-fold with placebo versus 4.5-fold with IL-7, P = .02) and lymph nodes (1.8-fold with placebo versus 4.1-fold with IL-7, P = .10) but not the thymus (3.4-fold with placebo versus 1.1-fold with IL-7, P = .18). Side effects of IL-7 included thrombocytopenia and possibly neutropenia and hemolytic anemia. One IL-7-treated animal failed to thrive due to a disease resembling graft-versus-host disease. No animals developed lymphoma. Bone density was not decreased. In conclusion, IL-7 raises CD4 T-cell counts in irradiated primates. It remains to be determined whether this is associated with clinical benefit.
引用
收藏
页码:4209 / 4218
页数:10
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