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 language | English |
|---|---|
| Pages (from-to) | 451-457 |
| Number of pages | 7 |
| Journal | Bone Marrow Transplantation |
| Volume | 23 |
| Issue number | 5 |
| Publication status | Published - 1999 |
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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 journal › Article
}
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 -