R. Aspinall, A POTENTIAL MECHANISM OF ACTION OF AN ANTIBODY (HIS45) WHICH HAS BEENSHOWN TO INDUCE PROLONGED GRAFT-SURVIVAL, Immunobiology, 196(4), 1996, pp. 425-436
Animals treated with the antibody HIS45 According to a regimen known t
o prolong the survival of allogeneic skin grafts (1), show no signific
ant decrease in alpha beta(+) T cells from their lymph nodes and no dr
amatic change in the levels of either alpha beta(+)CD4(+) or alpha bet
a(+)CD8(+) cells compared with untreated controls. However, the T cell
s of treated animals showed reduced expression of the alpha beta form
of the T cell receptor. Although treatment did not lead to an upregula
tion of the CD25 molecule on the rat cells, treatment does lead to a r
eduction at the cell surface in the amount of the determinant recogniz
ed by HIS45. lit vitro analysis revealed that the HIS45 determinant wa
s lost from T cells following their activation but re-expressed later.
The T cells in treated animals may be partially activated. This abili
ty of HIS45 to partially activate cells was supported by experiments w
hich revealed that the antibody HIS45 was only weakly mitogenic in vit
ro, but when present in conjunction with another stimulus such as anti
-V beta cell receptor antibody or a mitogen or a superantigen, the HIS
45 antibody was shown to produce significantly increased proliferation
. Functional analysis of cells from treated animals showed they respon
d significantly less well in vitro to either superantigen (TSST-1) or
alloantigen, compared to cells from age and sex matched untreated cont
rols. Since no T cell depletion occurred following treatment the reduc
ed functional ability of these cells must have been due to a functiona
l defect in their ability to respond. The results suggest thar HIS45 w
as having its immunosuppresive effect by delivering an incomplete acti
vation signal to T cells leading to a state of anergy.