Low-dose IL-2 for In vivo expansion of CD4+ and CD8+ regulatory T cells in nonhuman primates.
IL-2 is a known potent T cell growth factor that amplifies lymphocyte responses in vivo. This capacity has led to the use of high-dose IL-2 to enhance T cell immunity in patients with AIDS or cancer. However, more recent studies have indicated that IL-2 is also critical for the development and peripheral expansion of regulatory T cells (Tregs). In the current study, low-dose IL-2 (1 million IU/m(2) BSA/day) was administered to expand Tregs in vivo in naïve nonhuman primates. Our study demonstrated that low-dose IL-2 therapy significantly expanded peripheral blood CD4(+) and CD8(+) Tregs in vivo with limited expansion of non-Treg cells. These expanded Tregs are mainly CD45RA(-) Foxp3(high) activated Tregs and demonstrated potent immunosuppressive function in vitro. The results of this preclinical study can serve as a basis to develop Treg immunotherapy, which has significant therapeutic potential in organ/cellular transplantation.
Transplant Center, Massachusetts General Hospital, Harvard Medical School, Boston, USA.
A
A
Aoyama
D
D
Klarin
Y
Y
Yamada
S
S
Boskovic
O
O
Nadazdin
K
K
Kawai
D
D
Schoenfeld
J C
JC
Madsen
A B
AB
Cosimi
G
G
Benichou
T
T
Kawai
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D007376:Interleukin-2 / Q000008:administration & dosage / Q000494:pharmacology*; D008252:Macaca fascicularis; D008297:Male; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology
D007376:Interleukin-2