Induction of T cell anergy is thought to occur during activation in th
e absence of adequate costimulation, Here we demonstrate induction of
anergy in a CD8 T cell clone by its cognate Ag in the presence of B7-1
and B7-2 costimulation, Primary activation of a CD28(+)CD8(+) T cell
clone by either human T cell lymphotrophic virus type I (HTLV-I) Tax11
-19 peptide-pulsed EBV-transformed B cells, CD40L-stimulated B cells,
or T cells was sufficient to induce complete unresponsiveness to a sec
ondary Ag challenge. This was not caused by lack of B7 costimulation s
ince the APCs expressed B7-1 and B7-2 and failed to induce anergy in a
n MBP peptide 84-102-reactive CD4 T cell clone, While anergic CD8 T ce
lls did not proliferate, they retained their ability to lyse peptide-p
ulsed target cells. However, Ag stimulation failed to induce IL-2 mRNA
transcription and IL-2 secretion, although immediate early tyrosine p
hosphorylation was normal and anti-CD3 cross-linking induced identical
levels of CD40L expression in anergized and non-anergized CD8 T cells
. Secondary Ag stimulation in the presence of exogenous IL-2, however,
resulted in normal proliferative response. Moreover, while stimulatio
n of CD8 T cells with PHA and B cells induced anergy, CD8 T cell stimu
lation with PHA and mononuclear cells failed to do so. In addition, th
e presence of mononuclear cells during the exposure of CD8 T cells to
peptide-pulsed B cells prevented the induction of anergy, Together, ou
r observations demonstrate that at least a subpopulation of CD8 T cell
s are anergized when costimulation is provided by B cells or T cells.