TY - JOUR
T1 - 4-1BB promotes long-term survival in skin allografts treated with anti-CD45RB and anti-CD40L monoclonal antibodies
AU - Lee, J.
AU - Lee, E. N.
AU - Kim, E. Y.
AU - Lee, H. J.
AU - Park, H. J.
AU - Sun, C. L.
AU - Lee, S. K.
AU - Joh, J. W.
AU - Lee, K. W.
AU - Kwon, G. Y.
AU - Kim, S. J.
PY - 2005
Y1 - 2005
N2 - 4-1BB (CD137) is a T-cell co-stimulatory molecule that promotes T cell activation. Using a skin transplantation model, we observed that simultaneous administration of monoclonal antibodies (mAb) targeting CD45RB and CD40L prolonged skin allograft in co-stimulation blockade (CTLA4-Ig and anti-CD40L mAb)-resistant mice, because of reducing CD8+ T cells and CD4 + CD45RBhigh T cells. Anti-CD45RB mAb (45RB) blocks the activation of T helper 1 (Th1) cells and generates regulatory T cells (T reg). The experimental design included five groups: group 1, control; group 2, 45RB-MR1; group 3, 45B-MR1 + 4-IBBL; group 4, anti-CD4 mAb plus group 3 treatment; group 5, anti-CD8 mAb plus group 3 treatment. In this study we highlight the involvement of 4-1BB/4-1BBL in the development of T-cell responses. C57BL/6 recipients of BALB/c skin grafts were treated with 45RB, anti-CD40L mAb (MR1), and antagonistic anti-4-1BBL mAb (4-1BBL) on days 0, 2, 4, 6, and 8 posttransplantation. Additional 4-1BBL further prolonged skin graft survival, although the percentage of splenocyte-derived CD8+ T cells was reduced similarly in both groups. Use of 4-1BBL seems to have additive effects on Treg cells, which play a major role in the maintenance of tolerance. Even after immunosuppressive therapy in combination with CD4 + T-cell depletion, we did not achieve prolonged graft survival, possibly because of the absense of Treg cells, which require CD4-independent CD8+ T cells, based on the observation of increasing proportion of CD8+ T cells in similar degree as the control group.
AB - 4-1BB (CD137) is a T-cell co-stimulatory molecule that promotes T cell activation. Using a skin transplantation model, we observed that simultaneous administration of monoclonal antibodies (mAb) targeting CD45RB and CD40L prolonged skin allograft in co-stimulation blockade (CTLA4-Ig and anti-CD40L mAb)-resistant mice, because of reducing CD8+ T cells and CD4 + CD45RBhigh T cells. Anti-CD45RB mAb (45RB) blocks the activation of T helper 1 (Th1) cells and generates regulatory T cells (T reg). The experimental design included five groups: group 1, control; group 2, 45RB-MR1; group 3, 45B-MR1 + 4-IBBL; group 4, anti-CD4 mAb plus group 3 treatment; group 5, anti-CD8 mAb plus group 3 treatment. In this study we highlight the involvement of 4-1BB/4-1BBL in the development of T-cell responses. C57BL/6 recipients of BALB/c skin grafts were treated with 45RB, anti-CD40L mAb (MR1), and antagonistic anti-4-1BBL mAb (4-1BBL) on days 0, 2, 4, 6, and 8 posttransplantation. Additional 4-1BBL further prolonged skin graft survival, although the percentage of splenocyte-derived CD8+ T cells was reduced similarly in both groups. Use of 4-1BBL seems to have additive effects on Treg cells, which play a major role in the maintenance of tolerance. Even after immunosuppressive therapy in combination with CD4 + T-cell depletion, we did not achieve prolonged graft survival, possibly because of the absense of Treg cells, which require CD4-independent CD8+ T cells, based on the observation of increasing proportion of CD8+ T cells in similar degree as the control group.
UR - https://www.scopus.com/pages/publications/20144389526
U2 - 10.1016/j.transproceed.2005.01.016
DO - 10.1016/j.transproceed.2005.01.016
M3 - Article
C2 - 15808569
AN - SCOPUS:20144389526
SN - 0041-1345
VL - 37
SP - 123
EP - 125
JO - Transplantation Proceedings
JF - Transplantation Proceedings
IS - 1
ER -
