Some control data are available for adult patients, but there are relatively few data available for paediatric populations. References values for Vβ domain usage in healthy controls are essential for interpreting Vβ usage in disease states. Some suggest a diverse repertoire with overlap of T reg repertoire with normal CD4 +CD25 – cells, whereas others have suggested that T regs express different TCRs which are usually self-reactive. Studies examining the TCR repertoire of CD4 +CD25 + T regs have varied. Generation of T regs from FoxP3 – T cells has been described, although the role of this in vivo remains unclear. The forkhead box P3 transcription factor (FoxP3) has been identified as the key gene required for generation of these so-called natural T regulatory cells (T regs). ĬD4 +CD25 + T cells are crucial mediators of peripheral immune tolerance and are able to suppress T cells in a cell-contact dependent manner. Monoclonal antibodies to TCR Vβ families are now available covering > 70% of the whole TCR Vβ repertoire. Flow cytometric analysis has advantages in that it is a rapid, relatively inexpensive test that is reproducible between laboratories and gives quantitative information within different T cell subsets. CDR3 length spectratyping and flow cytometric analysis of TCR Vβ families labelled with specific monoclonal antibodies are the most frequently used assays for the analysis of TCR Vβ repertoire. TCR repertoire analysis has been used for studying selective T cell responses in autoimmune diseases, transplantation, immune deficiency and protective immunity against tumour and microbial antigens. Īnalysis of the TCR repertoire plays a crucial role in understanding the evolution and role of TCR diversity in immune responses. A complete TCR repertoire is indicative of an intact T cell population with the ability to recognize a wide range of immunogens. The majority of peripheral blood T lymphocytes express the αβ-TCR receptor comprising a heterodimer of α- and β-chains. TCRs are formed by random recombination of TCR gene elements and junctional region diversity during T cell intrathymic maturation, a process which allows for an extensive TCR repertoire, and the diversity of TCRs in a human at any given time has been estimated to be up to > 2 × 10 7. T lymphocytes recognize antigens presented by self-major histocompatibility complex (MHC) molecules via the T cell receptor (TCR). However, there was a significant preferential usage for five Vβ families and decreased usage of two Vβ families in the CD4 +CD25 Bright T cells, suggesting that although they overlap there may be subtle but important differences in the TCR repertoire of T regulatory cells. We found overlapping quantitative usage for each of the Vβ families between CD4 +CD25 – and CD4 +CD25 Bright T cells. We went on to examine the repertoire of CD4 +CD25 Bright T regulatory cells in 25 healthy controls. Some controls showed expansions in some Vβ families, although incidence of such expansions was low. Importantly, there appeared to be no significant change in Vβ usage according to age group. We found non-random Vβ usage with skewed reactivity of some families towards CD4 + or CD4 – T cells.
We examined the T lymphocyte (sub)populations in 47 healthy controls (age range: 3 months−16 years). For the interpretation of these studies information is needed about Vβ usage in healthy individuals and there are few data for normal usage in paediatric populations. Evaluation of the T cell receptor (TCR) Vβ repertoire by flow cytometric analysis has been used for studying the T cell compartments for diseases in which T cells are implicated in the pathogenesis.
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