Rapid modifications of peripheral T-cell subsets that express CD127 in macaques treated with recombinant IL-7

Abstract

Background: Interleukin-7 (IL-7) is a key regulator of thymopoiesis and T-cell homeostasis, which increases blood T-cell number by enhancing thymic output of naive cells and peripheral proliferation.

Methods: We explored the effects of unglycosylated recombinant simian IL-7 (rsIL-7) administration on peripheral T-cell subpopulations in healthy macaques.

Results: RsIL-7 was well tolerated. Mean half-life ranged between 9.3 and 13.9 hours. Blood CD3(+)CD4(+) and CD3(+)CD8(+) lymphocyte counts decreased rapidly after each rsIL-7 administration, the duration of these effects being dependent on the frequency of administration. At treatment completion, the increased of CD3(+) lymphocytes was marked at 100 microg/kg every 2 days. CD3(+) lymphocytes that harbour the alpha chain of IL-7 receptor (CD127) and CD3(+)CD8(+) lymphocytes that expressed the proliferation marker Ki-67 exhibited a similar initial profile. The expression of the anti-apoptotic marker Bcl-2 increased in CD3(+) lymphocytes during the treatment and post-treatment period in a dose/frequency dependent manner.

Conclusion: RsIL-7 was well tolerated in macaques and induces rapid modifications of T-cells that express CD127.