Activation-induced cytidine deaminase expression in CD4+ T cells is associated with a unique IL-10-producing subset that increases with age.
Activation-induced cytidine deaminase (AID), produced by the Aicda gene, is essential for the immunoglobulin gene (Ig) alterations that form immune memory. Using a Cre-mediated genetic system, we unexpectedly found CD4(+) T cells that had expressed Aicda (exAID cells) as well as B cells. ExAID cells increased with age, reaching up to 25% of the CD4(+) and B220(+) cell populations. ExAID B cells remained IgM(+), suggesting that class-switched memory B cells do not accumulate in the spleen. In T cells, AID was expressed in a subset that produced IFN-γ and IL-10 but little IL-4 or IL-17, and showed no evidence of genetic mutation. Interestingly, the endogenous Aicda expression in T cells was enhanced in the absence of B cells, indicating that the process is independent from the germinal center reaction. These results suggest that in addition to its roles in B cells, AID may have previously unappreciated roles in T-cell function or tumorigenesis.
Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Hongyan
H
Qin
Keiichiro
K
Suzuki
Mikiyo
M
Nakata
Shunsuke
S
Chikuma
Nakako
N
Izumi
Le Thi
le T
Huong
Mikako
M
Maruya
Sidonia
S
Fagarasan
Meinrad
M
Busslinger
Tasuku
T
Honjo
Hitoshi
H
Nagaoka
D000375:Aging / Q000097:blood*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology* / Q000378:metabolism; D003564:Cytidine Deaminase / Q000097:blood* / Q000235:genetics; D016753:Interleukin-10 / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D012333:RNA, Messenger; D016753:Interleukin-10; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase