Previously we have shown that peripheral expansion but not de novo generation of CD4 T cells was improved in baboons treated with human IL-7 (Storek et al: Blood 101:4209, 2003). However, in that study at least 2 animals developed neutralizing anti-human IL-7 antibodies, only moderately lymphopenic animals were treated, and the treatment was given for only 1 month. The current study was undertaken to evaluate the effect of baboon-specific IL-7, given for 2 months, to severely lymphopenic animals.

Seven baboons were rendered lymphopenic by total body irradiation and ATG. Three baboons received placebo and four baboons received recombinant baboon IL-7 (80 ug/kg/d subcutaneously, kind gift of Cytheris, Vanves, France).

During treatment, the median of average weekly CD4 T cell counts was 1081/ul in the IL-7 treated group vs 384/ul in the placebo group (p=0.06, one-tailed). This appeared to be a result of peripheral expansion rather than de novo generation as the absolute number of circulating TREC-containing CD4 T cells in the two groups was similar. To evaluate if the increase in CD4 T cell number was functionally relevant, we enumerated CMV-specific CD4 T cells - cells secreting IFN-gamma upon stimulation with baboon CMV viral lysate. During the second months of treatment, the IL-7-treated baboons had higher numbers of circulating CMV-specific CD4 T cells than the placebo-treated baboons (median of weekly averages, 85 vs 1 cell/ul, p=0.03).

In lymphopenic primates IL-7 can increase the number of CD4 T cells, including functional anti-viral CD4 T cells.