T-Cell Receptor Vβ Repertoire CDR3 Length Diversity Differs within CD45RA and CD45RO T-Cell Subsets in Healthy and Human Immunodeficiency Virus-Infected Children

Kou, Zhong Chen; Puhr, Joshua S.; Rojas, Mabel; McCormack, Wayne T.; Goodenow, Maureen M.; Sleasman, John W.

doi:10.1128/cdli.7.6.953-959.2000

Cited by 34 publications

(39 citation statements)

References 32 publications

(22 reference statements)

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“…Similar oligoclonal repertoires were detected by CDR3 V␤ analysis of CD8 ϩ , but not CD4 ϩ T cell populations in two nude/SCID patients tested 6 years after BMT, suggesting a differential maintenance of CD4 ϩ and CD8 ϩ TCR repertoire complexity (37). The CD8 ϩ CD45RO ϩ cells may be Ag-specific effector T cells directed against Ags to which the individuals are exposed or they may represent regulatory T cells (25,38). The reason why the oligoclonality developed mainly in the CD8 ϩ T cell subset is unclear at the present time, although it has been previously reported in normal subjects (23).…”

Section: Figure 7 Cd8mentioning

confidence: 66%

T Cell Repertoire Development in Humans with SCID After Nonablative Allogeneic Marrow Transplantation

Sarzotti¹,

Patel

Li³

et al. 2003

The Journal of Immunology

101

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Transplantation of HLA-identical or haploidentical T cell-depleted allogeneic bone marrow (BM) into SCID infants results in thymus-dependent T cell development in the recipients. Immunoscope analysis of the TCR Vβ repertoire was performed on 15 SCID patients given BM transplants. Before and within the first 100 days after bone marrow transplantation (BMT), patients’ PBMC displayed an oligoclonal or skewed T cell repertoire, low TCR excision circles (TREC) values, and a predominance of CD45RO+ T cells. In contrast, the presence of high numbers of CD45RA+ cells in the circulation of SCID patients >100 days post-BMT correlated with active T cell output by the thymus as revealed by high TREC values and a polyclonal T cell repertoire demonstrated by a Gaussian distribution of Vβ-specific peaks. Ten years after BMT, we observed a decrease of the normal polyclonal T cell repertoire and an increase of a more skewed T cell repertoire. A decline of TREC levels and a decrease in the number of CD45RA+ cells beyond 10 years after BMT was concomitant with the detection of oligoclonal CD3+CD8+CD45RO+ cells. The switch from a polyclonal to a more skewed repertoire, observed in the CD3+CD8+CD45RO+ T cell subset, is a phenomenon that occurs normally with decreased thymic output during aging, but not as rapidly as in this patient population. We conclude that a normal T cell repertoire develops in SCID patients as a result of thymic output and the repertoire remains highly diverse for the first 10 years after BMT. The TCR diversity positively correlates in these patients with TREC levels.

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Section: Figure 7 Cd8mentioning

confidence: 66%

T Cell Repertoire Development in Humans with SCID After Nonablative Allogeneic Marrow Transplantation

Sarzotti¹,

Patel

Li³

et al. 2003

The Journal of Immunology

101

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“…Thirdly, analysis of CDR3 length diversity can be used to define the extent of clonal expansion within the TCR repertoire. 42,43 The TCR V␤ CDR3 complexity decreased in CD8 ϩ T cells with diminished CD8␤ expression. The results suggest that CD8␣ ϩ ␤ low and, moreover, CD8␣␣ ␣␤ T cells have proliferated extensively probably by antigenic stimulations.…”

Section: Discussionmentioning

confidence: 99%

CD8αα memory effector T cells descend directly from clonally expanded CD8α+βhigh TCRαβ T cells in vivo

Konno

Okada

Mizuno

et al. 2002

Blood

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“…Peak areas were quantified and normalized with the size marker to determine the total normalized area corresponding to each Vb family. To assess the presence of monoclonal T cell expansions, the relative fluorescence intensity (RI) was calculated: RI (%) = (peak area/total Vb area) (33,34). A CDR3 peak with an RI .…”

Section: Cdr3 Length Analysis By Spectratypingmentioning

confidence: 99%

TCR Bias of In Vivo Expanded T Cells in Pancreatic Islets and Spleen at the Onset in Human Type 1 Diabetes

Codina-Busqueta

Scholz

Torres

et al. 2011

The Journal of Immunology

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Autoreactive T cells, responsible for the destruction of pancreatic β cells in type 1 diabetes, are known to have a skewed TCR repertoire in the NOD mouse. To define the autoreactive T cell repertoire in human diabetes, we searched for intraislet monoclonal expansions from a recent onset in human pancreas to then trace them down to the patient’s peripheral blood and spleen. Islet infiltration was diverse, but five monoclonal TCR β-chain variable expansions were detected for Vβ1, Vβ7, Vβ11, Vβ17, and Vβ22 families. To identify any sequence bias in the TCRs from intrapancreatic T cells, we analyzed 139 different CDR3 sequences. We observed amino acid preferences in the NDN region that suggested a skewed TCR repertoire within infiltrating T cells. The monoclonal expanded TCR sequences contained amino acid combinations that fit the observed bias. Using these CDR3 sequences as a marker, we traced some of these expansions in the spleen. There, we identified a Vβ22 monoclonal expansion with identical CDR3 sequence to that found in the islets within a polyclonal TCR β-chain variable repertoire. The same Vβ22 TCR was detected in the patient’s PBMCs, making a cross talk between the pancreas and spleen that was reflected in peripheral blood evident. No other pancreatic monoclonal expansions were found in peripheral blood or the spleen, suggesting that the Vβ22 clone may have expanded or accumulated in situ by an autoantigen present in both the spleen and pancreas. Thus, the patient’s spleen might be contributing to disease perpetuation by expanding or retaining some autoreactive T cells.

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T-Cell Receptor Vβ Repertoire CDR3 Length Diversity Differs within CD45RA and CD45RO T-Cell Subsets in Healthy and Human Immunodeficiency Virus-Infected Children

Cited by 34 publications

References 32 publications

T Cell Repertoire Development in Humans with SCID After Nonablative Allogeneic Marrow Transplantation

T Cell Repertoire Development in Humans with SCID After Nonablative Allogeneic Marrow Transplantation

CD8αα memory effector T cells descend directly from clonally expanded CD8α+βhigh TCRαβ T cells in vivo

TCR Bias of In Vivo Expanded T Cells in Pancreatic Islets and Spleen at the Onset in Human Type 1 Diabetes

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