CD69 cell surface expression identifies developing thymocytes which audition for T cell antigen receptor-mediated positive selection

Yamashita, Iwao; Nagata, Toshi; Tada, Tomio; Nakayama, Toshinori

doi:10.1093/intimm/5.9.1139

Cited by 207 publications

(176 citation statements)

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“…3). As previously described [20], thymocytes from untreated mice showed a small percentage of CD69 + cells (10-15%). Treatment with isotype-matched control mAb 2.8 did not affect CD69 + cells, whereas treatment with mAb 2.2 reduced the expression of CD69 to negligible levels, similar to those seen in CD69 -/-mice (Fig.…”

Section: Cd69-deficient Mice Develop a Normal Arthritis Response To Asupporting

confidence: 68%

The role of CD69 in acute neutrophil‐mediated inflammation

et al. 2006

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The leukocyte activation marker CD69 functions as a negative regulator of the immune response, both in NK-dependent tumor rejection and in the inflammation associated with lymphocyte-dependent collagen-induced arthritis. In contrast, it has been reported that CD69-deficient mice are refractory to the neutrophil-dependent acute inflammatory response associated with anti-type II collagen antibody-induced arthritis (CAIA), suggesting a positive regulatory role for CD69 in neutrophil function during arthritis induction. To clarify this discrepancy, the CAIA response was independently analyzed in our CD69-deficient mice. In these experiments, the inflammatory response was unaffected by CD69 deficiency. Additionally, the in vivo down-regulation of CD69 expression by treatment of wild-type mice with the anti-CD69 mAb 2.2, which mimics the CD69-deficient phenotype, did not affect the course of arthritis in this model. Moreover, down-regulation of CD69 expression increased expression in arthritic joints of key inflammatory mediators, including IL-1b, IL-6 and the chemokine MCP-1. Neutrophil accumulation in zymosan-treated air pouches and in thioglycolate-treated peritoneal cavities was also unaffected in CD69-deficient mice. In addition, CD69 expression was absent in activated neutrophils. Taken together, these results rule out a significant stimulatory role for CD69 in acute inflammatory responses mediated by neutrophils.

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Section: Cd69-deficient Mice Develop a Normal Arthritis Response To Asupporting

confidence: 68%

The role of CD69 in acute neutrophil‐mediated inflammation

et al. 2006

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“…However, the same multi-phasic pattern of TCR expression was observed. We studied another surrogate marker of TCR engagement, CD69, which is transiently up-regulated after TCR signaling [41,42]. In C10.4 + /1.11 TEC cultures a rapid increase of CD69 levels was observed at both AttM concentrations (610 pM and 625 nM) (Fig.…”

Section: Thymocyte Selection Is Multi-phasicmentioning

confidence: 99%

Maturational stage-dependent thymocyte responses to TCR engagement

Kattman¹,

Lukin²,

Oh³

et al. 2005

Eur. J. Immunol.

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Thymocyte positive and negative selection are dependent on avidity-driven TCRmediated recognition events in the thymus. High-avidity recognition events result in negative selection, while low-avidity recognition events result in positive selection. However, it has not been established how thymocytes maturation stages affect their responses to TCR signals of different avidities. We gained insight into this question when we reduced thymocyte selection to an in vitro system, in which full maturation of developmentally synchronized immature double-positive thymocytes was induced on a cloned line of thymic epithelial cells. Our analysis of the kinetics of thymocyte development supports a multi-phasic model of thymic selection. In it, thymocyte maturation stages as well as interaction avidity control the outcome TCR stimulation. Positive selection is initiated during a primary recognition event that proceeds independently of the TCR avidity. During a secondary recognition event the final fate of thymocyte, full maturation versus negative selection, is determined by TCR avidity.

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“…These results suggest that the quantity of TCR signal directly regulates positive and negative selection, and further suggests that weaker signals direct positively selected T cells to the CD8 lineage and stronger signals to the CD4 lineage. To ensure that these CD4 ϩ or CD8 ϩ SP thymocytes had undergone positive selection, thymocytes from OVA-administered DOTg/ KO mice (150 M) were stained with the maturity markers, HSA and CD69 (24,25). Onsets of HSA down-regulation and CD69 up-regulation are closely correlated with positive selection.…”

Section: Quantity Of Tcr Signal Determines Cd4/cd8 Lineage Commitmentmentioning

confidence: 99%

The Quantity of TCR Signal Determines Positive Selection and Lineage Commitment of T Cells

Watanabe

Arase

Onodera

et al. 2000

The Journal of Immunology

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It is generally accepted that the avidity of TCR for self Ag/MHC determines the fate of immature thymocytes. However, the contribution of the quantity of TCR signal to T cell selection has not been well established, particularly in vivo. To address this issue, we analyzed DO-TCR transgenic CD3ζ-deficient (DO-Tg/ζKO) mice in which T cells have a reduced TCR on the cell surface. In DO-Tg/ζKO mice, very few CD4 single positive (SP) thymocytes developed, indicating that the decrease in TCR signaling resulted in a failure of positive selection of DO-Tg thymocytes. Administration of the peptide Ag to DO-Tg/ζKO mice resulted in the generation of functional CD4 SP mature thymocytes in a dose-dependent manner, and, unexpectedly, DO-Tg CD8 SP cells emerged at lower doses of Ag. TCR signal-dependent, sequential commitment from CD8+ SP to CD4+ SP was also shown in a class I-restricted TCR-Tg system. These in vivo analyses demonstrate that the quantity of TCR signal directly determines positive and negative selection, and further suggest that weak signal directs positively selected T cells to CD8 lineage and stronger signal to CD4 lineage.

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CD69 cell surface expression identifies developing thymocytes which audition for T cell antigen receptor-mediated positive selection

Cited by 207 publications

References 0 publications

The role of CD69 in acute neutrophil‐mediated inflammation

The role of CD69 in acute neutrophil‐mediated inflammation

Maturational stage-dependent thymocyte responses to TCR engagement

The Quantity of TCR Signal Determines Positive Selection and Lineage Commitment of T Cells

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