Objective. To study thymus-dependent T cell development and T cell repertoire in human s ever com-bined immunodeficiencypatients after HLA-identical or haploid entical T cell-depleted allogeneic bone marrow transplant...Objective. To study thymus-dependent T cell development and T cell repertoire in human s ever com-bined immunodeficiencypatients after HLA-identical or haploid entical T cell-depleted allogeneic bone marrow transplantation.Methods .Blood samples were obtained from15SCID patients before transplantation and a t varying intervals thereafter.Quantitative competitive PCR assay and immunosco pe analysis of the T cell receptorVarepertoire were performed.Results. Before and within the first100days after transplantation,patients’ periphera l blood mononuclear cellpresented an oligoclonal or polyclonal skewed T cell repertoire,low T cell re-ceptor excision circlesvalues and pred ominance of CD45RO + T cell.In contrast,the presence of high numbers of CD45RA + T cells in bone marrowcirculation reconstituted SCID patients(>10 0days post-transplantation)correlated with active T cell production by the th ymus as revealed by high TREC values,and a polyclonal T cell repertoire demonst rated by a Gaussian distribution of Va-specific peaks.Conclusions.Within one year after BMT ,a normal T cell repertoire develops in SCID patients as a resu lt of thymic output.The T cell receptor diversity is highly and positively corr elated in these patients with TREC levels.展开更多
文摘Objective. To study thymus-dependent T cell development and T cell repertoire in human s ever com-bined immunodeficiencypatients after HLA-identical or haploid entical T cell-depleted allogeneic bone marrow transplantation.Methods .Blood samples were obtained from15SCID patients before transplantation and a t varying intervals thereafter.Quantitative competitive PCR assay and immunosco pe analysis of the T cell receptorVarepertoire were performed.Results. Before and within the first100days after transplantation,patients’ periphera l blood mononuclear cellpresented an oligoclonal or polyclonal skewed T cell repertoire,low T cell re-ceptor excision circlesvalues and pred ominance of CD45RO + T cell.In contrast,the presence of high numbers of CD45RA + T cells in bone marrowcirculation reconstituted SCID patients(>10 0days post-transplantation)correlated with active T cell production by the th ymus as revealed by high TREC values,and a polyclonal T cell repertoire demonst rated by a Gaussian distribution of Va-specific peaks.Conclusions.Within one year after BMT ,a normal T cell repertoire develops in SCID patients as a resu lt of thymic output.The T cell receptor diversity is highly and positively corr elated in these patients with TREC levels.
