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Induction of Alloantigen-specific Anergy in Human Peripheral Blood Mononuclear Cells by Alloantigen Stimulation with Co-stimulatory Signal Blockade
Published on: March 14, 2011
Effects of superantigenic stimulation on the cord blood alphabeta T cell repertoire
A Toubert1, C Douay, N Chalumeau
1INSERM U 396, Institut Biomédical des Cordeliers et Centre G Hayem, Hôpital Saint-Louis, Paris, France.
Umbilical cord blood (CB) constitutes a promising alternative to bone marrow for allogeneic transplantation and is most remarkable for the reduced severity of GVHD compared with bone marrow. We have shown that although naive the TCR beta-chain repertoire appears fully constituted at birth in terms of mean size of the complementarity-determining region 3 (CDR3) and of the usage of V and J gene segments. Its ability to respond to exogenous stimuli was tested with staphylococcal superantigens TSST-1 and SEA (toxin at 1 ng/ml for 4 days). The amount of TCR transcripts was quantified and the percentage of representation of each BV family was calculated. TSST-1 induced BV2 expansion in both adult and CB samples. SEA activation gave a more variable pattern among individuals (adults n = 6; CB n = 6). BV6, BV18, BV22 and BV24 were the most frequently expanded families. We did not observe notable differences in either the modification of the TCRBV repertoire or the kinetics of the response to SEA superantigen between adults and newborns. These data suggest that although naive, CB lymphocytes are as equally capable as adult lymphocytes of responding to superantigen stimulation.
Umbilical cord blood (CB) constitutes a promising alternative to bone marrow for allogeneic transplantation and is most remarkable for the reduced severity of GVHD compared with bone marrow. We have shown that although naive the TCR beta-chain repertoire appears fully constituted at birth in terms of mean size of the complementarity-determining region 3 (CDR3) and of the usage of V and J gene segments. Its ability to respond to exogenous stimuli was tested with staphylococcal superantigens TSST-1 and SEA (toxin at 1 ng/ml for 4 days). The amount of TCR transcripts was quantified and the percentage of representation of each BV family was calculated. TSST-1 induced BV2 expansion in both adult and CB samples. SEA activation gave a more variable pattern among individuals (adults n = 6; CB n = 6). BV6, BV18, BV22 and BV24 were the most frequently expanded families. We did not observe notable differences in either the modification of the TCRBV repertoire or the kinetics of the response to SEA superantigen between adults and newborns. These data suggest that although naive, CB lymphocytes are as equally capable as adult lymphocytes of responding to superantigen stimulation.
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