Expression of genes encoding the pre-TCR and CD3 complex during thymus development

MacDonald, H. Robson; Malissen, Bernard

doi:10.1093/intimm/7.10.1659

Cited by 65 publications

(61 citation statements)

References 34 publications

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“…On the whole, these findings lend strong support to the idea that T lineage-committed precursors, which match the developmental stage of triple-negative c-Kit high CD44 ϩ CD25 low/Ϫ thymocytes before pre-T␣ gene transcription (34,35), but after expression of CD3⑀-specific mRNA (35,36), are present in gut CP (30). One impediment to this conclusion has been the detection of a marginal level of RAG-2 transcripts for CP lymphocytes (22).…”

Section: Linsupporting

confidence: 65%

Intestinal γδ T Cells Develop in Mice Lacking Thymus, All Lymph Nodes, Peyer’s Patches, and Isolated Lymphoid Follicles

Nonaka

Naito

Chen

et al. 2005

The Journal of Immunology

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Through analysis of athymic (nu/nu) mice carrying a transgenic gene encoding GFP instead of RAG-2 product, it has recently been reported that, in the absence of thymopoiesis, mesenteric lymph nodes and Peyer’s patches (PP) but not gut cryptopatches are pivotal birthplace of mature T cells such as the thymus-independent intestinal intraepithelial T cells (IEL). To explore and evaluate this important issue, we generated nu/nu mice lacking all lymph nodes (LN) and PP by administration of lymphotoxin-β receptor-Ig and TNF receptor 55-Ig fusion proteins into the timed pregnant nu/+ mice that had been mated with male nu/nu mice (nu/nu LNP− mice). We also generated nu/nu aly/aly (aly, alymphoplasia) double-mutant mice that inherently lacked all LN, PP, and isolated lymphoid follicles. Although γδ-IEL were slightly smaller in number than those in nu/nu mice, substantial colonization of γδ-IEL was found to take place in the intestinal epithelia of nu/nu LNP− and nu/nu aly/aly mice. Notably, the population size of a major CD8αα+ γδ-IEL subset was maintained, the use of TCR-γ-chain variable gene segments by these γδ-IEL was unaltered, and the development of cryptopatches remained intact in these nu/nu LNP− and nu/nu aly/aly mice. These findings indicate that all LN, including mesenteric LN, PP, and isolated lymphoid follicles, are not an absolute requirement for the development of γδ-IEL in athymic nu/nu mice.

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Section: Linsupporting

confidence: 65%

Intestinal γδ T Cells Develop in Mice Lacking Thymus, All Lymph Nodes, Peyer’s Patches, and Isolated Lymphoid Follicles

Nonaka

Naito

Chen

et al. 2005

The Journal of Immunology

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“…It is thus possible that TRIM may have a function in pre-TCR-initiated proliferation of fetal thymocytes, although its detectability at dg 16.5 is not in perfect agreement with the onset of proliferation. In adult thymopoesis, the TRIM expression in DN2 precedes that of TCRb polypeptide chains, of pre-Ta and of CD31 in DN3 [14,42], consistent with but not strongly indicative for an involvement in pre-TCR signalling. Thus, the onset of TRIM expression is not in striking correlation with the pre-TCR/CD3 dependent developmental checkpoints in fetal or adult thymopoesis.…”

Section: Discussionmentioning

confidence: 68%

“…Lck for which the mRNA is seen as early as DN1 but the protein expression occurs as late as DN3 [14,39,42]. Moreover, in fetal thymocytes granzyme A and B mRNAs have been observed without the corresponding proteins being detectable by enzymatic activity [43].…”

Section: Discussionmentioning

confidence: 99%

Developmentally Regulated Expression of the Transmembrane Adaptor Protein TRIM in Fetal and Adult T Cells

et al. 2001

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TRIM is a recently identified transmembrane adaptor protein which is exclusively expressed in T cells and natural killer (NK) cells. In peripheral blood T cells TRIM has been reported to coprecipitate, comodulate, and cocap with the T‐cell receptor (TCR), suggesting that it is an integral component of the TCR/CD3/ζ complex. Here we investigate the expression of TRIM mRNAs and proteins in developing thymocytes. Two splicing isoforms with open reading frames are observed, namely a full length (TRIM) and a truncated version (ΔTM‐TRIM). The latter lacks the extracellular and transmembrane domains as well as the first 10 cytoplasmic aminoacids and is significantly expressed only as mRNA in early fetal thymocytes. TRIM mRNA is detected in all mainstream thymocyte subsets in adult mice. TRIM protein, in contrast, first appears in the DN2 (CD44+ CD25+) subset of adult double negative (DN) cells. In fetal thymocyte development, TRIM mRNA is seen from dg 14.5 onwards whereas TRIM protein appears first on dg 16.5. In contrast to the adult, the TRIM protein was seen in a subset of fetal DN1 cells. In fetal and adult thymocytes, TRIM protein expression was highest in DN2, DN3 (CD44−25+) and in DP cells, compatible with a functional role at or around phases of thymic selection.

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“…These include ordered intracellular assembly and transport to the cell surface, receptor-induced differential signal transduction, and receptor internalization (ligand-induced and independent). CD3 chain specific transcripts are expressed as early as DN1 stage and almost all the DN3 thymocytes express high amounts of clonotype independent CD3␥ and CD3␦ complexes (CIC) (13). Despite very high levels of intracellular expression, very negligible amount of CICs are expressed on the DN3 thymocytes, indicating the presence of strong ER retention motifs in these CD3 chains.…”

Section: Cd8mentioning

confidence: 99%

Critical and Multiple Roles for the CD3ε Intracytoplasmic Tail in Double Negative to Double Positive Thymocyte Differentiation

Brodeur

Li²,

Martins³

et al. 2009

The Journal of Immunology

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The preTCR is associated with signal-transducing CD3␥, ␦, , and polypeptides. It is generally agreed that CD3 chains play redundant roles in the receptor-mediated signal transduction. In the present study, we show that the intracytoplasmic (IC) domain of CD3 is essential for early thymocyte maturation. We demonstrate that the IC domain-deleted CD3 fails to restore the double negative (DN) to double positive (DP) thymocyte development in CD3-deficient mice. Additional experiments show that the membrane proximal basic amino acid rich sequence in the IC domain of CD3 is sufficient for the DN to DP differentiation, whereas the proline rich sequence is required for efficient proliferation. This is probably due to impaired ligand independent recruitment of Nck to the proline rich sequence motif of CD3 within the context of the preTCR. The data presented in this study elucidates mechanistic basis for the preTCR-induced proliferation of the DN thymocytes and have identified distinct roles for individual motifs of CD3 in the preTCR-mediated differentiation and proliferation. These data provide the first genetic and phenotypic evidence for requirement of the IC domain of a CD3 chain in thymocyte development. ϩ (double positive or DP) and thymic selection of the DP thymocytes results in the generation of CD4ϩ (single positive or SP). The preTCR, which consists of a pT␣/TCR␤ heterodimer and signal transducing invariant CD3␥-, ␦-, -, and -chains, mediates the DN to DP transition (1-3). The preTCR is expressed at a low level on the DN thymocytes and is suggested to be due to the endoplasmic reticulum (ER) retention and constitutive internalization of the surface receptor (4 -7). It is generally agreed that the preTCR functions in a ligand-independent manner. The oligomerization of preTCR via the pT␣-chain has been proposed as the mechanism for the preTCR-mediated cell autonomous signal transduction (8). The surface expression of the preTCR initiates multiple intracellular signaling pathways, culminating in the DN to DP differentiation and clonal expansion, resulting in a several-fold increase in thymic cellularity (3). Several studies suggest that the preTCR-mediated differentiation and clonal expansion of the DN thymocytes are two distinct processes (reviewed in Ref. 9). Thus, transgenic expression of dominant-negative fas-associated death domain, or abrogation of either early growth response gene 3 or c-Myc transcription factor impairs proliferation, but not differentiation, of the DN thymocytes (10 -12). However, it is not clear whether the preTCR is capable of directly inducing multiple pathways each resulting in distinct biological processes.CD3 chains play multiple roles in the preTCR-mediated DN to DP thymocyte differentiation. These include ordered intracellular assembly and transport to the cell surface, receptor-induced differential signal transduction, and receptor internalization (ligand-induced and independent). CD3 chain specific transcripts are expressed as early as DN1 stage and almost all the DN3 thymocytes e...

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Expression of genes encoding the pre-TCR and CD3 complex during thymus development

Cited by 65 publications

References 34 publications

Intestinal γδ T Cells Develop in Mice Lacking Thymus, All Lymph Nodes, Peyer’s Patches, and Isolated Lymphoid Follicles

Intestinal γδ T Cells Develop in Mice Lacking Thymus, All Lymph Nodes, Peyer’s Patches, and Isolated Lymphoid Follicles

Developmentally Regulated Expression of the Transmembrane Adaptor Protein TRIM in Fetal and Adult T Cells

Critical and Multiple Roles for the CD3ε Intracytoplasmic Tail in Double Negative to Double Positive Thymocyte Differentiation

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