FACTORS THAT INFLUENCE ACTIVATED CD8(-CELL APOPTOSIS IN PATIENTS WITHACUTE HERPESVIRUS INFECTIONS - LOSS OF COSTIMULATORY MOLECULES CD28, CD5 AND CD6 BUT RELATIVE MAINTENANCE OF BAX AND BCL-X EXPRESSION() T)

The expanded CD8(+) T-lymphocyte population arising in response to vir al infection controls the virus but could also prove damaging to the h ost unless safely removed at the end of the immune response. Apoptosis provides a mechanism whereby this can be achieved, as apoptotic cells are recognized and engulfed by macrophages. Peripheral blood CD8(+) T lymphocytes from individuals with acute viral infections were highly susceptible to apoptosis after short-term culture in vitro. This spont aneous cell death could be prevented by interleukin-2 (IL-2) and was r elated to a decreased expression of Bcl-2 but not Pax or Bcl-X(L), add itional molecules that promote or prevent apoptosis, respectively, as well as an increase in CD95. After stimulation with anti-CD3 antibody, T cells from these patients also underwent an activation-induced cell death (AICD) that could not be prevented by IL-2. Interestingly, CD8( +) T cells from this patient group expressed lower than normal levels of three costimulatory molecules, CD28, CD5 and CD6, suggesting that s timulation in the absence of a second signal is a possible mechanism f or the defective reactivation of these cells. Thus multiple mechanisms , including loss of Bcl-2, increased CD95 and loss of costimulatory mo lecules, place constraints on the survival and reactivation of activat ed CD8(+) T cells after viral infections. This enables immune activati on to be controlled and cellular homeostasis to be reestablished durin g resolution of viral diseases in vivo.