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

25 Citations (Scopus)

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

Fingerprint

Lymphocyte Activation
Bone Marrow Transplantation
Cell Death
Apoptosis
T-Lymphocytes
Mitogens
Regeneration
Lymphocytes
T-Lymphocyte Subsets
HLA-DR Antigens
Interleukin-2
Down-Regulation
Phenotype

Keywords

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

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

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. / Brugnoni, D.; Airò, P.; Pennacchio, M.; Carella, G.; Malagoli, A.; Ugazio, A. G.; Porta, F.; Cattaneo, R.

In: Bone Marrow Transplantation, Vol. 23, No. 5, 1999, p. 451-457.

Research output: Contribution to journalArticle

@article{e590bfca507546288dad88f50bfd494a,
title = "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",
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.",
keywords = "Apoptosis, Bcl-2, Bone marrow transplant, Fas, Severe combined immunodeficiency",
author = "D. Brugnoni and P. Air{\`o} and M. Pennacchio and G. Carella and A. Malagoli and Ugazio, {A. G.} and F. Porta and R. Cattaneo",
year = "1999",
language = "English",
volume = "23",
pages = "451--457",
journal = "Bone Marrow Transplantation",
issn = "0268-3369",
publisher = "Nature Publishing Group",
number = "5",

}

TY - JOUR

T1 - Immune reconstitution after bone marrow transplantation for combined immunodeficiencies

T2 - Down-modulation of Bcl-2 and high expression of CD95/Fas account for increased susceptibility to spontaneous and activation-induced lymphocyte cell death

AU - Brugnoni, D.

AU - Airò, P.

AU - Pennacchio, M.

AU - Carella, G.

AU - Malagoli, A.

AU - Ugazio, A. G.

AU - Porta, F.

AU - Cattaneo, R.

PY - 1999

Y1 - 1999

N2 - 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.

AB - 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.

KW - Apoptosis

KW - Bcl-2

KW - Bone marrow transplant

KW - Fas

KW - Severe combined immunodeficiency

UR - http://www.scopus.com/inward/record.url?scp=0032976288&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032976288&partnerID=8YFLogxK

M3 - Article

C2 - 10100558

AN - SCOPUS:0032976288

VL - 23

SP - 451

EP - 457

JO - Bone Marrow Transplantation

JF - Bone Marrow Transplantation

SN - 0268-3369

IS - 5

ER -