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, P. Airò, M. Pennacchio, G. Carella, A. Malagoli, A. G. Ugazio, F. Porta, R. Cattaneo

Research output: Contribution to journalArticle

Abstract

We have studied the regeneration of T cell subsets and function after BMT in 21 children affected by combined immunodeficiency after BMT. In the first months, the striking predominance of CD4+ cells displayed the primed CD45R0+ phenotype and a high number of activated (HLA-DR+)T cells were observed.Regeneration of naive CD4+CD45RA+ cells correlated with the recovery 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-induced cell death (AICD) after restimulation with mitogens. In accordance with the role of CD95/Fas in this latter process, we have observed a high level 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 cells and decreased with the progressive recovery of T cell proliferative response. Therefore, the lymphocyte hyperactivated status might explain their susceptibility to apoptosis and contribute to the genesis of immunodeficiency that follows BMT.

Original languageEnglish
Pages (from-to)451-457
Number of pages7
JournalBone Marrow Transplantation
Volume23
Issue number5
Publication statusPublished - 1999

Keywords

  • Apoptosis
  • Bcl-2
  • Bone marrow transplant
  • Fas
  • Severe combined immunodeficiency

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Fingerprint Dive into the research topics of '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'. Together they form a unique fingerprint.

  • Cite this