Enhanced susceptibility to apoptosis in T cells recovering after autologous peripheral blood progenitor cell transplantation: Reversal by interleukin-15

T-cell number and competence are profoundly impaired after transplantation of autologous cytokine-mobilized peripheral blood progenitor cells (PBPC). The objective of the present study was to evaluate the occurrence of T-cell spontaneous apoptosis (A(spont)) and its modulation in vitro by the interl eukin-2 receptor (IL-2R) gamma -chain (gammac)-signaling cytokine interieuk in-15 (IL-15) in the peripheral blood of patients transplanted with autolog ous PBPC for hematological malignancies. An average 45% +/- 6% of CD4(+) an d 55% +/- 6% of CD8(+) T cells cultured in the absence of exogenous cytokin es underwent A(spont); of interest, IL-15 and, to a lesser extent, its stru ctural cousin IL-2 counteracted T-cell A(spont) and upregulated Bcl-2 level s. IL-15 did not rescue T cells from A(spont) by promoting proliferation, b ut rather it acted as a genuine survival factor. Furthermore, T-cell preinc ubation with a gammac-blocking antibody was capable of abrogating both apop tosis inhibition and Bcl-2 induction by IL-15. These in vitro findings sugg est that IL-15 might represent a promising immunomodulating agent to improv e T-cell function after autologous PBPC transplantation.