DIFFERENTIAL REQUIREMENTS FOR COSTIMULATORY SIGNALS FROM B7 FAMILY MEMBERS BY RESTING VERSUS RECENTLY ACTIVATED MEMORY T-CELLS TOWARDS SOLUBLE RECALL ANTIGENS
Yq. Zhang et al., DIFFERENTIAL REQUIREMENTS FOR COSTIMULATORY SIGNALS FROM B7 FAMILY MEMBERS BY RESTING VERSUS RECENTLY ACTIVATED MEMORY T-CELLS TOWARDS SOLUBLE RECALL ANTIGENS, International immunology, 8(1), 1996, pp. 37-44
The interaction between CD28 on T cells with CD80 (B7-1) and CD86 (B7-
2) on APCs is considered to be of critical importance for primary T ce
ll activation both in vivo and in vitro. The relative importance of th
is co-stimulatory signal in memory T cell activation is, however, less
clear, and was therefore studied by in vitro experiments on T cell re
sponses to soluble recall antigens using peripheral blood mononuclear
cells or T cell clones, Our data demonstrate that B7-2 represents the
major co-stimulatory signal for the activation of resting peripheral b
lood memory T cells with recall antigens, as evidenced by the effects
of anti-B7-1 and anti-B7-2 on T cell proliferation as well as on IL-2
and INF-gamma production, Since CTLA-4-Ig and anti-CD28 Fab fragments
had similar inhibitory effects to the combination of anti-B7-1 plus an
ti-B7-2, the involvement of a third cc-stimulatory CD28/CTLA-4 ligand
is unlikely, Despite the strong effects of B7-blocking agents, a varia
ble fraction of the memory T cells was resistant to inhibition. Moreov
er, T cell clones or in vitro preactivated T cells could efficiently b
e restimulated by soluble antigens on autologous APCs in the absence o
f B7-1 or B7-2 co-stimulation. These data show that most memory T cell
s that are freshly isolated from the blood are still dependent on CD28
triggering for their activation. However, recently activated T cells
can apparently bypass the requirement for B7 and use other costimulato
ry signals for reactivation, a finding with important implications for
the development of immunosuppressive strategies.