TCR‐β chains derived from peripheral γδ T cells can take part in αβ T‐cell development

Abstract

Between 10 and 20% of the peripheral cd T cells express cytoplasmic TCR-b proteins, but whether such TCR-b chains can partake in ab T-cell development has never been systematically investigated. Therefore, we reconstituted the T-cell compartment of CD3e-deficient mice with Pax5-TCR-b deficient proB cells expressing, via a retroviral vector, TCR-b chains from either peripheral cd or ab T cells. Recipient thymi reconstituted with proB cells containing empty vector were small (o15 Â 10 6 cells), contained few cd T but no ab T cells. In contrast, thymi from mice receiving proB cells containing cd or ab T-cellderived TCR-b chains contained 80-130 Â 10 6 cells, and showed a normal CD4, CD8 and ab TCR expression pattern. However, regardless of the source of TCR-b chain, reconstituted mice rapidly showed signs of autoimmunity dying 5-15 wk following reconstitution. Autoimmune disease induction could be prevented by co-transfer of Treg cells thereby allowing the functionality of the generated T cells to be assessed. Results obtained show that TCR-b chains from cd T cells can efficiently take part in ab T-cell development. The implications of these findings for cd T-cell development will be discussed.Key words: ab T cells . gd T cells . TCR-b chains . pre-TCR . Thymus Supporting Information available online Introduction T-cell development takes place in the thymus from progenitors of bone marrow origin. By now it is generally believed that a cell called a thymus settling progenitor (TSP), characterized by the expression of CD44, CD117, CD135 and the chemokine receptor CCR9 [1][2][3][4] is the bone marrow cell that enters the thymus. However, transplantation experiments in T-cell-deficient mice have indicated that other progenitors can enter the thymus and may take part in T-cell development [2,5,6].Early T-cell progenitors in the thymus lack CD4 and CD8 expression and are therefore called double negative (DN) cells. Based on the differential expression of CD44, CD25 and CD117, DN cells can be subdivided into DN1-4 subpopulations. Thus DN1 cells are CD44 + , CD25 À and CD117 High and within this population, TSP are included as a CD135 + subpopulation [2,4,7,8]. DN1 cells differentiate through a CD44 + , CD25 + , CD117 high DN2 stage to become CD44 À , CD25 + , CD117 À/low DN3 cells [8].Ã These authors contributed equally to this work. 3520Both DN1 and DN2 cells still possess multi-lineage developmental potential, including that for NK, dendritic and myeloid cells [9][10][11] whereas B-cell lineage potential seems to be restricted to the TSP population within the DN1 subset [1,2,4,7]. By largely unknown mechanisms, commitment to the T-cell lineage is acquired at the DN2 to DN3 cell transition [9,12]. However, cells at the DN3 stage still have the option to develop into either ab or gd T-cell lineage cells [13][14][15]. A relatively large number of studies have indicated that the expression of the pre-TCR plays a crucial role in the development of ab T cells [14][15][16]. Recent, elegant, single cell studies have indicated ...

In vivo fate mapping identifies pre-TCRα expression as an intra- and extrathymic, but not prethymic, marker of T lymphopoiesis

“…2 D). Lack of pT expression in  precursor cells can thus be formally excluded as an explanation for the presence of functional TCR chains in a significant percentage of  T cells (Bosco et al, 2008). pT iCre expression is confined to T progenitors lacking B cell, NK cell, and myeloid lineage potential If pT was expressed in a T lineage precursor population with physiologically relevant CLP activity, as suggested previously intermediate progenitors (CIPs) to be described below.…”

A population of proinflammatory T cells coexpresses αβ and γδ T cell receptors in mice and humans

“…However, aberrant expression of TCR chains has been demonstrated among αβ and γδ T cell populations ( Bowen et al, 2014 ; Hochstenbach and Brenner, 1989 ; Ishida et al, 1990 ). For example, in-frame TCRδ rearrangements have been identified in αβ T cells ( Livak et al, 1995 ), and functional TCRβ rearrangements have been detected in γδ T cells ( Bosco et al, 2008 ). The latter may even confer a proliferative advantage and selectively amplify certain subsets of murine TCRβ + γδ thymocytes ( Wilson and MacDonald, 1998 ).…”

Human Peripheral CD4+ Vδ1+ γδT Cells Can Develop into αβT Cells

“…In order to exclude these observations as artifacts of ex vivo culture systems, we compared our findings with established literature data, and in order to identify its physiological relevance, we aimed to show analogs of this new developmental pathway in vivo . Several groups of researchers have shown that around 10–20% of all peripheral γδ T cells transcribe and express in-frame TCR-β rearrangements ( 63 – 65 ) that can guide αβT-cell development, resulting in fully functional, mature T cells ( 66 ). Consistent with these findings, CD4 + Vδ1 + clones transcribed in-frame TCR-β chain rearrangements, showed cytoplasmic protein expression of TCR-β chains, and expressed the TCR-β chain on their cell surface as they bound BMA031.…”