Immune reconstitution after bone marrow transplantation for combined immunodeficiencies: down-modulation of Bcl-2 and high expression of CD95/Fas account for increased susceptibility to spontaneous and activation-induced lymphocyte cell death
D. Brugnoni et al., Immune reconstitution after bone marrow transplantation for combined immunodeficiencies: down-modulation of Bcl-2 and high expression of CD95/Fas account for increased susceptibility to spontaneous and activation-induced lymphocyte cell death, BONE MAR TR, 23(5), 1999, pp. 451-457
Citations number
34
Categorie Soggetti
Hematology,"Medical Research Diagnosis & Treatment
We have studied the regeneration of T cell subsets and function after BMT i
n 21 children affected by combined immunodeficiency after BMT, Zn the first
months, the striking predominance of CD4(+) cells displayed the primed CD4
5R0(+) phenotype and a high number of activated (HLA-DR+)T cells were obser
ved, Regeneration of naive CD4(+)CD45RA(+) cells correlated with the recove
ry of proliferative responses to mitogens (r = 0.64, P < 0.001). Peripheral
blood lymphocytes circulating after BMT undergo an increased process of in
vitro cell death, resulting from two mechanisms: spontaneous apoptosis (SA
), a consequence of defective production of IL-2 and down-regulation of Bcl
-2 (P = 0.02 vs healthy controls), and high susceptibility to activation-in
duced cell death (AICD) after restimulation with mitogens, In accordance wi
th the role of CD95/Fas in this latter process, we have observed a high lev
el of CD95 expression (P < 0.001 vs healthy controls), correlated with AICD
(P < 0.001) but not with SA, and decreasing with time after BMT (P < 0.001
). Both SA and AICD levels correlated with the presence of activated T cell
s and decreased with the progressive recovery of T cell proliferative respo
nse. Therefore, the lymphocyte hyperactivated status might explain their su
sceptibility to apoptosis and contribute to the genesis of immunodeficiency
that follows BMT.