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Prepublished online as a Blood First Edition Paper on January 23, 2003; DOI 10.1182/blood-2002-08-2671.

Submitted September 3, 2002
Accepted January 6, 2003
Interleukin-7 improves CD4 T cell reconstitution after autologous CD34 cell transplantation in monkeys
Jan Storek*, Thurman Gillespy, Hailing Lu, Ansamma Joseph, Monja A Dawson, Michael Gough, Julia Morris, Robert C Hackman, Peter A Horn, George E Sale, Robert G Andrews, David G Maloney, and Hans-Peter Kiem
Fred Hutchinson Cancer Research Center, Seattle, WA, USA; University of Washington, Seattle, WA, USA
* Corresponding author; email: jstorek{at}fhcrc.org.
In mice, interleukin-7 (IL7) hastens T cell reconstitution, and might cause autoimmune diseases, lymphoma and osteoporosis. We assessed the effect of IL7 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 three baboons received recombinant human IL7 (rhIL7, 75 µg/kg twice a day subcutaneously) between 6 and 10 weeks after transplant. Mean increase in blood absolute CD4 T cell counts was 0.9-fold in the placebo-treated animals versus 9.0-fold in the IL7-treated animals (p=.02). The increase observed in the IL7-treated animals appeared attributable to peripheral expansion rather than de novo generation. The IL7-treated animals had greater mean increases in the volumes of the spleen (2.0-fold with placebo versus 4.5-fold with IL7, p=.02) and lymph nodes (1.8-fold with placebo versus 4.1-fold with IL7, p=.10) but not the thymus (3.4-fold with placebo versus 1.1-fold with IL7, p=.18). Side effects of IL7 included thrombocytopenia, and possibly neutropenia and hemolytic anemia. One IL7-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, IL7 raises CD4 T cell counts in irradiated primates. It remains to be determined whether this is associated with clinical benefit.

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