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


CONCLUSIONS
RsIL-7 was well tolerated in macaques and induces rapid modifications of T-cells that express CD127.
Dereuddre-Bosquet
Nathalie
N
SPI-BIO, CEA, Fontenay-aux-Roses, Cedex, France.
Vaslin
Bruno
B
Delache
Benoit
B
Brochard
Patricia
P
Clayette
Pascal
P
Aubenque
Céline
C
Morre
Michel
M
Assouline
Brigitte
B
Le Grand
Roger
R
D000818:Animals; D005434:Flow Cytometry / Q000662:veterinary; D006207:Half-Life; D015851:Interleukin-7 / Q000493:pharmacokinetics / Q000494:pharmacology*; D053699:Interleukin-7 Receptor alpha Subunit / Q000096:biosynthesis / Q000276:immunology*; D018655:Lymphocyte Count; D008252:Macaca fascicularis / Q000276:immunology*; D008297:Male; D011897:Random Allocation; D011994:Recombinant Proteins / Q000493:pharmacokinetics / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
D015851:Interleukin-7; D053699:Interleukin-7 Receptor alpha Subunit; D011994:Recombinant Proteins