Estimating Thymic Function Through Quantification of T-Cell Receptor Excision Circles

Dion, Marie-Lise; Sékaly, Rafick‐Pierre; Cheynier, Rémi

doi:10.1385/1-59745-395-1:197

Cited by 17 publications

(29 citation statements)

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“…In RAG2p-GFP mice, the mitotic history of thymocytes can be assessed by analyzing the amount of GFP and sjTRECs in discrete cell subsets. Following rearrangement of TCRa-chains (in CD4 + CD8 + thymocytes), the amount of GFP per cell progressively decreases (15), and each cell division decreases the frequency of sjTREC + cells by 50% (23). We found that the three populations of GFP + CD8 + thymocytes (CD44 lo , CD44 int and CD44 hi ) contained similar amounts of GFP and sjTRECs (Fig.…”

Section: Statistical Analysesmentioning

confidence: 53%

Development and Function of Innate Polyclonal TCRαβ+ CD8+ Thymocytes

Rafei

Hardy

Williams

et al. 2011

The Journal of Immunology

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Innate CD8 T cells are found in mutant mouse models, but whether they are produced in a normal thymus remains controversial. Using the RAG2p-GFP mouse model, we found that ∼10% of TCRαβ+ CD4−CD8+ thymocytes were innate polyclonal T cells (GFP+CD44hi). Relative to conventional T cells, innate CD8 thymocytes displayed increased cell surface amounts of B7-H1, CD2, CD5, CD38, IL-2Rβ, and IL-4Rα and downmodulation of TCRβ. Moreover, they overexpressed several transcripts, including T-bet, Id3, Klf2, and, most of all, Eomes. Innate CD8 thymocytes were positively selected, mainly by nonhematopoietic MHCIa+ cells. They rapidly produced high levels of IFN-γ upon stimulation and readily proliferated in response to IL-2 and IL-4. Furthermore, low numbers of innate CD8 thymocytes were sufficient to help conventional CD8 T cells expand and secrete cytokine following Ag recognition. This helper effect depended on CD44-mediated interactions between innate and conventional CD8 T cells. We concluded that innate TCRαβ+ CD8 T cells represent a sizeable proportion of normal thymocytes whose development and function differ in many ways from those of conventional CD8 T cells.

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Section: Statistical Analysesmentioning

confidence: 53%

Development and Function of Innate Polyclonal TCRαβ+ CD8+ Thymocytes

Rafei

Hardy

Williams

et al. 2011

The Journal of Immunology

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“…TRAV, TRBD, and TRBJ were numbered according to the nomenclature described by the international ImMunoGeneTics information system (http://imgt.cines.fr). Real-time PCR quantification of the different TRECs were performed using LightCycler technology (Roche Diagnostics) as previously described, (31) and using the CD4 gene as a housekeeping gene. Briefly, cells were lysed in Tris-HCl (pH 8.3; 10 mM), Tween 20 (0.05%), and Nonidet P-40 (0.05%) supplemented with proteinase K (100 g/ml) for 30 min at 56°C.…”

Section: Trec Quantificationmentioning

confidence: 99%

“…This method is based on the simultaneous measurement of sjTREC, generated by the deletion of the TCR␦ locus before rearrangement of the TCR␣ sequences, and that of TRECs generated during TCR␤ chain rearrangement (DJ␤TRECs, byproducts of the rearrangement between TRBD and TRBJ segments). In humans, the ratio of these two types of TREC was estimated as a marker for intrathymic precursor T cell proliferation and thus used as a surrogate marker for thymic output (9,(31)(32)(33)(34).…”

Section: Measuring Trecs and The Sj/␤trec Ratio In Micementioning

confidence: 99%

The Magnitude of Thymic Output Is Genetically Determined through Controlled Intrathymic Precursor T Cell Proliferation

Dulude

Cheynier

Gauchat

et al. 2008

The Journal of Immunology

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The thymus plays a crucial role in providing the immune system with naive T cells showing a diverse TCR repertoire. Whereas the diversity of thymic production is mainly ensured by TCR rearrangement at both the TRA and TRB loci, the number of cells reaching the double-positive differentiation stage defines the extent of thymic output. A quantitative analysis of TCR excision circles (TREC; signal-joint TRECs and DJβTRECs) produced at different stages of thymopoiesis was performed in nine laboratory mouse strains. The results clearly demonstrate that the magnitude of thymic output is directly proportional to the extent of proliferation in the double-negative 4 thymocyte subset. Strikingly, intrathymic precursor T cell proliferation was found to be strain dependent, thus suggesting a genetic regulation of thymic output. The inherited character of thymic output was further confirmed by the transmission of the phenotype in a recessive fashion in F1 progeny of the different parental strains. Our results provide the first demonstration of the genetic regulation of thymic output.

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“…Indirect evidence of the impact of antiretroviral therapy on recovery of the thymus has been obtained through imaging studies and measurements of TRECs (Dion et al, 2007;Halnon et al, 2005;Lee et al, 2006;McCune et al, 1998 andreviewed in (Ho Tsong Fang et al, 2005)). It is clear that the thymus plays an important role in HIV infection and in the regeneration of naïve CD4 + T cells.…”

Section: Discussionmentioning

confidence: 99%