Dendritic cells derived from TBP-2-deficient mice are defective in inducing T cell responses.
Thioredoxin-binding protein-2 (TBP-2), also known as vitamin D3-up-regulated protein 1 (VDUP1), was identified as an endogenous molecule interacting with thioredoxin (TRX). Here, we show that dendritic cells (DC) derived from TBP-2-deficient mice are defective in the function of T cell activation. To compare TBP-2(-/-) DC function with wild-type (WT) DC, we stimulated DC with lipopolysaccharide (LPS). Although TBP-2(-/-) DC and WT DC expressed comparable levels of MHC class II and costimulatory molecules such as CD40, CD80 and CD86, the IL-12p40, IL-12p70 and IL-6 productions of TBP-2(-/-) DC were attenuated. In a mixed leukocyte reaction (MLR), the concentrations of IL-2, IFN-gamma, IL-4 and IL-10 in the culture supernatant of MLR with TBP-2(-/-) DC were significantly lower than those in the cultures with WT DC. In MLR also, as with LPS stimulation, IL-12p40 and IL-12p70 production from TBP-2(-/-) DC was less than that from WT DC. Proliferation of T cells cultured with TBP-2(-/-) DC was poorer than that with WT DC. In vivo delayed-type hypersensitivity responses in TBP-2(-/-) mice immunized with ovalbumin were significantly reduced compared to WT mice. These results indicate that TBP-2 plays a crucial role in DC to induce T cell responses.
Son
Aoi
A
Department of Biological Responses, Institute for Virus Research, Kyoto University, Kyoto, Japan. aoison@virus.kyoto-u.ac.jp
Nakamura
Hajime
H
Okuyama
Hiroaki
H
Oka
Shin-ichi
S
Yoshihara
Eiji
E
Liu
Wenrui
W
Matsuo
Yoshiyuki
Y
Kondo
Norihiko
N
Masutani
Hiroshi
H
Ishii
Yasuyuki
Y
Iyoda
Tomonori
T
Inaba
Kayo
K
Yodoi
Junji
J
D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002352:Carrier Proteins / Q000502:physiology*; D049109:Cell Proliferation; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D005260:Female; D015870:Gene Expression; D006968:Hypersensitivity, Delayed / Q000139:chemically induced / Q000235:genetics / Q000276:immunology; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D013879:Thioredoxins / Q000502:physiology*
D002352:Carrier Proteins; D016207:Cytokines; D015850:Interleukin-6; D008070:Lipopolysaccharides; C445672:Txnip protein, mouse; D018664:Interleukin-12; D013879:Thioredoxins; D010047:Ovalbumin