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Glycosylated recombinant simian IL-7 induces sustained increased in peripheral
naïve and memory T cell counts in healthy Rhesus macaques: a new possibility for
immune reconstitution
Stéphanie Beq, Clémentine Shilte, David Gautier, Xavier Montagutelli, Pascal Lavedan,
Michel Brahic and Rémi Cheynier
Institut Pasteur, Paris, France
IL-7 is a crucial cytokine for both thymopoiesis and peripheral T cell homeostasis. Treating
SIV-infected and non-infected macaques with RmIL-7 leads to a transient increase of
circulating T cells, due to both enhanced thymopoiesis and increased peripheral T cell
proliferation. However, the effect of non-glycosylated IL-7 is systematically blunted by the
rapid development of a strong neutralizing anti-IL-7 immune response. In this study, we
investigated the impact of a single dose (100 µg/kg) of glycosylated recombinant simian
IL-7 (RmIL-7gly) on T cell homeostasis in healthy Rhesus macaques. Using 8 parameters
flow cytometry and real time PCR for the quantification of the signal joint T cell receptor
excision circle (sjTREC), we followed the frequency and the absolute numbers as well as
the cycling and the survival capacity of the different peripheral T cell subsets : CD4, CD8,
naives, memory, effector and recent thymic emigrants (RTEs, as defined by high
expression of CD31 in naïve CD4 T cell subset and sjTREC frequency) during the first
days following RmIL-7gly injection. Within the first 24 hours following RmIL-7gly injection
we observed a strong decline of all T cell subsets in both CD4 and CD8 compartments.
The analysis of T cell subsets in lymph nodes suggests that this decrease was a
consequence of T cell homing into secondary lymphoid organs. Following this initial
period, all T cell subsets demonstrate a strong expression of Ki-67 (30 to 90%).
This proliferation leads to an expansion of the T cell subpopulations by day 4-7, reaching
higher values than in pre-treatment samples. Finally, the absolute number of circulating
RTEs began to increase by day 7, leading to a 5- to 10-fold increase at day 14 post
RmIL-7gly. This was confirmed by the quantification of the sjTREC molecule in peripheral
blood of the animals. A second injection in the same animals was performed 3 months
after the first one. Similar modifications of peripheral T cell homeostasis were observed.
Finally, contrarily to the non glycosylated molecule, RmIL-7gly did not induce the
development of IL-7 specific antibodies. The administration of a single dose of RmIL-7gly
both stimulates thymic function leading to enhanced RTE frequency and induces an
increase of peripheral naïve and memory subset numbers in healthy Rhesus macaques,
suggesting that HuIL-7gly might be used to help HIV-infected patients to recover from
lymphopenia under efficient antiretroviral therapy.
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