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 (Aspont) and its modulation in vitro by the interleukin-2 receptor (IL-2R) gamma-chain (gammac)-signaling cytokine interleukin-15 (IL-15) in the peripheral blood of patients transplanted with autologous PBPC for hematological malignancies. An average 45%+/-6% of CD4+ and 55%+/-6% of CD8+ T cells cultured in the absence of exogenous cytokines underwent Aspont; of interest, IL-15 and, to a lesser extent, its structural cousin IL-2 counteracted T-cell Aspont and upregulated Bcl-2 levels. IL-15 did not rescue T cells from Aspont by promoting proliferation, but rather it acted as a genuine survival factor. Furthermore, T-cell preincubation with a gammac-blocking antibody was capable of abrogating both apoptosis inhibition and Bcl-2 induction by IL-15. These in vitro findings suggest that IL-15 might represent a promising immunomodulating agent to improve T-cell function after autologous PBPC transplantation.
Rutella
S
S
Department of Hematology, Catholic University Medical School, Rome, Italy. sergiorutella@tin.it
Bonanno
G
G
Pierelli
L
L
Sorà
F
F
Sica
S
S
Scambia
G
G
d'Onofrio
G
G
Rumi
C
C
Leone
G
G
D000328:Adult; D000941:Antigens / Q000378:metabolism; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D015536:Down-Regulation; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D016130:Immunophenotyping; D019409:Interleukin-15 / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D015375:Receptors, Interleukin-2 / Q000737:chemistry; D013601:T-Lymphocytes / Q000378:metabolism* / Q000473:pathology*; D015854:Up-Regulation
D000941:Antigens; D019409:Interleukin-15; D015375:Receptors, Interleukin-2