TY - JOUR
T1 - CD28-independent, TRAF2-dependent costimulation of resting T cells by 4- 1BB ligand
AU - Saoulli, Katina
AU - Lee, Soo Young
AU - Cannons, Jennifer L.
AU - Yeh, Wen Chen
AU - Santana, Angela
AU - Goldstein, Marni D.
AU - Bangia, Naveen
AU - DeBenedette, Mark A.
AU - Mak, Tak W.
AU - Choi, Yongwon
AU - Watts, Tania H.
PY - 1998/6/1
Y1 - 1998/6/1
N2 - 4-1BB ligand (4-1BBL) is a member of the tumor necrosis factor (TNF) family expressed on activated antigen-presenting cells. Its receptor, 4-1BB, is a member of the TNF receptor family expressed on activated CD4 and CD8 T cells. We have produced a soluble form of 4-1BBL using the baculovirus expression system. When coimmobilized on plastic with anti-CD3, soluble 4- 1BBL induces interleukin (IL)-2 production by resting CD28+ or CD28- T cells, indicating that 4-1BBL can function independently of other cell surface molecules, including CD28, in costimulation of resting T cell activation. At low concentrations of anti-CD3, 4-1BBL is inferior to anti- CD28 in T cell activation. However, when 4-1BB ligand is provided together with strong TCR signals, then 4-1BBL and anti-CD28 are equally potent in stimulation of IL-2 production by resting T cells. We find that TNF receptor- associated factor (TRAF)1 or TRAF2 associate with a glutathione S- transferase-4-1BB cytoplasmic domain fusion protein in vitro. In T cells, we find that association of TRAF1 and TRAF2 with 4-1BB requires 4-1BB cross- linking. In support of a functional role for TRAF2 in 4-1BB signaling, we find that resting T cells isolated from TRAF2-deficient mice or from mice expressing a dominant negative form of TRAF2 fail to augment IL-2 production in response to soluble 4-1BBL. Thus 4-1BB, via the TRAF2 molecule, can provide CD28-independent costimulatory signals to resting T cells.
AB - 4-1BB ligand (4-1BBL) is a member of the tumor necrosis factor (TNF) family expressed on activated antigen-presenting cells. Its receptor, 4-1BB, is a member of the TNF receptor family expressed on activated CD4 and CD8 T cells. We have produced a soluble form of 4-1BBL using the baculovirus expression system. When coimmobilized on plastic with anti-CD3, soluble 4- 1BBL induces interleukin (IL)-2 production by resting CD28+ or CD28- T cells, indicating that 4-1BBL can function independently of other cell surface molecules, including CD28, in costimulation of resting T cell activation. At low concentrations of anti-CD3, 4-1BBL is inferior to anti- CD28 in T cell activation. However, when 4-1BB ligand is provided together with strong TCR signals, then 4-1BBL and anti-CD28 are equally potent in stimulation of IL-2 production by resting T cells. We find that TNF receptor- associated factor (TRAF)1 or TRAF2 associate with a glutathione S- transferase-4-1BB cytoplasmic domain fusion protein in vitro. In T cells, we find that association of TRAF1 and TRAF2 with 4-1BB requires 4-1BB cross- linking. In support of a functional role for TRAF2 in 4-1BB signaling, we find that resting T cells isolated from TRAF2-deficient mice or from mice expressing a dominant negative form of TRAF2 fail to augment IL-2 production in response to soluble 4-1BBL. Thus 4-1BB, via the TRAF2 molecule, can provide CD28-independent costimulatory signals to resting T cells.
KW - 4-1BB
KW - Costimulation
KW - Signaling
KW - T cells
KW - TRAF2
UR - http://www.scopus.com/inward/record.url?scp=0032101119&partnerID=8YFLogxK
U2 - 10.1084/jem.187.11.1849
DO - 10.1084/jem.187.11.1849
M3 - Article
C2 - 9607925
AN - SCOPUS:0032101119
SN - 0022-1007
VL - 187
SP - 1849
EP - 1862
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 11
ER -