Background:  By sustaining thymopoiesis as well as peripheral T cell proliferation and survival interleukin (IL) -7 plays a crucial role in T cell homeostasis. Previous studies in macaque models have demonstrated that exogenous IL-7 induces the expansion of naive and memory T cell subsets from day 7 after injection. These observations have led to its use in phase I/II trial in chronically HIV-infected patients to counteract T cell lymphopenia. We here analyzed the early events occurring after simian recombinant glycosylated IL-7 (R-sIL-7gly) injection into healthy Rhesus macaques.

Methods:  A single dose (80 µg/kg of body weight) of R-sIL-7gly was subcutaneously injected in 2 healthy rhesus macaques, while healthy control animal received placebo. The same single administration was repeated 3 month later in the same animals. The first events following the few first hours post-injection were analyzed.

Results:  We observed for the first time a strong and rapid T cell migration out of the blood during the first hours following treatment. As early as 6 hours post injection, a vast majority (as much as 70%) of the circulating T cells had disappeared from the blood. This phenomenon concerned all T cell subsets, including recent thymic emigrants, naïve, central memory, and effector memory T cells in both CD4 and CD8 compartments. Concomitantly these T cells up-regulated several chemokine receptors implicated in homing mechanisms (CXCR4, CCR6, and CCR9, but not CCR7), while plasma concentration of a number of chemokines/cytokines (IL-8, IL-10, IL-1b, IL-1Ra, MIP-1b) implicated in migratory phenomena was significantly increased. Finally, immunohistochemical analysis allowed us to demonstrate that T cells migrating out from blood during the first hours following R-sIL-7 injection principally home into the gut.

Conclusions:  These data demonstrate that one of the first functions of circulating IL-7 might be to stimulate peripheral T cell migration into some epithelia, major sites of its production, in order to maximize signaling and homeostatic responses.