A Monoclonal Antibody Against the 66-kDa Protein Expressed in Mouse Spleen and Thymus Inhibits Ly-6A.2-Dependent Cell-Cell Adhesion

English, Andrea; Kosoy, Roman; Pawlinski, Rafel; Bamezai, Anil

doi:10.4049/jimmunol.165.7.3763

Cited by 28 publications

(25 citation statements)

References 35 publications

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“…Our previous reports suggest the presence of Ly-6A.2 ligand on the majority of B cells and macrophages (34,44). APC-dependent inhibition of CD4 ϩ Tg T cell responses to peptide Ag is consistent with these published data, because splenic APC is comprised of B cells and macrophages.…”

Section: Discussionsupporting

confidence: 79%

“…Although the ligands that might bind Ly-6 proteins have been proposed (44,45), the functional consequence of their interaction with Ly-6 proteins remains unclear. We demonstrate that Ly-6A.2 expression negatively regulates Ag-specific CD4 ϩ T cell responses by interacting with a candidate ligand.…”

Section: Discussionmentioning

confidence: 99%

“…One representative experiment of three experiments is shown. expressing cells to Ly-6A.2-overexpressing Chinese hamster ovary cells (44). We sought to test whether the anti-Ly-6A.2 ligand Ab reversed the peptide-specific hyporesponsiveness that was observed with Ly-6A.2 Tg CD4 ϩ T cells.…”

Section: Role Of Ly-6a2-ligand Interactions In Ag-specific Inhibitiomentioning

confidence: 99%

“…We recently reported biochemical characterization of a candidate ligand that binds Ly-6A.2 (44). The Ly-6A.2 candidate ligand is expressed on the majority of B cells and macrophages (Refs.…”

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confidence: 99%

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Ly-6A.2 Expression Regulates Antigen-Specific CD4+ T Cell Proliferation and Cytokine Production

Henderson

Kamdar

Bamezai

2002

The Journal of Immunology

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Ly-6 proteins appear to serve cell adhesion and cell signaling function, but the precise role of Ly-6A.2 in CD4+ T lymphocytes is still unclear. Overexpression of Ly-6A.2 in T lymphocytes has allowed us to analyze the influence of elevated Ly-6A.2 expression on T cell function. In this study we report reduced proliferation of CD4+ T cells overexpressing Ly-6A.2 in response to a peptide Ag. Moreover, the Ly-6A.2-overexpressing CD4+ cells generated elevated levels of IL-4, a key factor that propels the differentiation of naive CD4+ T cells into Th2 subset. The hyporesponsiveness of Ly-6A.2 transgenic CD4+ T cells is dependent on the interaction of Ly-6A.2 T cells with the APCs and can be reversed by blocking the interaction between Ly-6A.2 and a recently reported candidate ligand. Overexpression of Ly-6A.2 in CD4+ T cells reduced their Ca2+ responses to TCR stimulation, therefore suggesting effects of Ly-6A.2 signaling on membrane proximal activation events. In contrast to the observed Ag-specific hyporesponsiveness, the Ly-6A.2 transgenic CD4+ T cells produced IL-4 independent of the interactions between Ly-6A.2 and the candidate Ly-6A.2 ligand. Our results suggest that 1) interaction of Ly-6A.2 with a candidate ligand regulates clonal expansion of CD4+ Th cells in response to an Ag (these results also provide further functional evidence for presence of Ly-6A.2 ligand on APC); and 2) Ly-6A.2 expression on CD4+ T cells promotes production of IL-4, a Th2 differentiation factor.

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Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Section: Role Of Ly-6a2-ligand Interactions In Ag-specific Inhibitiomentioning

confidence: 99%

mentioning

confidence: 99%

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Ly-6A.2 Expression Regulates Antigen-Specific CD4+ T Cell Proliferation and Cytokine Production

Henderson

Kamdar

Bamezai

2002

The Journal of Immunology

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“…Ly-6A is expressed on pluripotent hematopoietic stem cells, developing thymocytes, and mature T cells (Spangrude et al, 1988;van de Rijn et al, 1989). Several studies have suggested a role for Ly-6A in T cell signaling and cell adhesion (English et al, 2000). A functional role for Ly-6A in myoblast differentiation, however, is unprecedented.…”

Section: Genes Expressed Only During Early Myoblast Differentiation Cmentioning

confidence: 99%

Genome‐wide examination of myoblast cell cycle withdrawal during differentiation

Shen

Collier

Hlaing

et al. 2002

Developmental Dynamics

105

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Skeletal and cardiac myocytes cease division within weeks of birth. Although skeletal muscle retains limited capacity for regeneration through recruitment of satellite cells, resident populations of adult myocardial stem cells have not been identified. Because cell cycle withdrawal accompanies myocyte differentiation, we hypothesized that C2C12 cells, a mouse myoblast cell line previously used to characterize myocyte differentiation, also would provide a model for studying cell cycle withdrawal during differentiation. C2C12 cells were differentiated in culture medium containing horse serum and harvested at various time points to characterize the expression profiles of known cell cycle and myogenic regulatory factors by immunoblot analysis. BrdU incorporation decreased dramatically in confluent cultures 48 hr after addition of horse serum, as cells started to form myotubes. This finding was preceded by up-regulation of MyoD, followed by myogenin, and activation of Bcl-2. Cyclin D1 was expressed in proliferating cultures and became undetectable in cultures containing 40% fused myotubes, as levels of p21 WAF1/Cip1 increased and ␣-actin became detectable. Because C2C12 myoblasts withdraw from the cell cycle during myocyte differentiation following a course that recapitulates this process in vivo, we performed a genome-wide screen to identify other gene products involved in this process. Using microarrays containing ϳ10,000 minimally redundant mouse sequences that map to the UniGene database of the National Center for Biotechnology Information, we compared gene expression profiles between proliferating, differentiating, and differentiated C2C12 cells and verified candidate genes demonstrating differential expression by RT-PCR. Cluster analysis of differentially expressed genes revealed groups of gene products involved in cell cycle withdrawal, muscle differentiation, and apoptosis. In addition, we identified several genes, including DDAH2 and Ly-6A, whose expression specifically was up-regulated during cell cycle withdrawal coincident with early myoblast differentiation. Developmental Dynamics 226:128 -138, 2003.

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Ly-6A is critical for the function of double negative regulatory T cells

2002

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We have recently demonstrated that CD3+CD4–CD8– double negative (DN) T cells can down‐regulate allogeneic immune responses both in vitro and in vivo by killing activated syngeneic CD8+ T cells. The goal of this study was to identify molecules that are crucial for DN T cell‐mediated suppression. We demonstrate that Ly‐6A (Sca‐1) is highly expressed on DN T cells. Incubation with IL‐10 significantly reduced Ly‐6A expression and the function of DN T cells. DN T cell‐mediated killing was significantly reduced when Ly‐6A was blocked.Ly‐6A‐deficient mice showed an accelerated allograft rejection when compared to wild‐type controls. Furthermore we demonstrate that pretransplantation donor lymphocyte infusion (DLI) led to activation and proliferation of recipient DN T cells and prolongation of bm1→B6 skin allograft survival. However, when the recipients were deficient in Ly‐6A, the beneficial effect of DLI on allograftsurvival was abolished. Moreover, deficiency in Ly‐6A did not affect the activation and proliferation of DN T cells. Rather, it impaired the ability of DN T cells to kill activated anti‐donor CD8+ Tcells. Taken together, our data indicate that Ly‐6A plays a crucial role in DN T cell‐mediated regulation in vitro and in vivo, perhaps by enhancing DN‐CD8+ T cell signaling.

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A Monoclonal Antibody Against the 66-kDa Protein Expressed in Mouse Spleen and Thymus Inhibits Ly-6A.2-Dependent Cell-Cell Adhesion

Cited by 28 publications

References 35 publications

Ly-6A.2 Expression Regulates Antigen-Specific CD4+ T Cell Proliferation and Cytokine Production

Ly-6A.2 Expression Regulates Antigen-Specific CD4+ T Cell Proliferation and Cytokine Production

Genome‐wide examination of myoblast cell cycle withdrawal during differentiation

Ly-6A is critical for the function of double negative regulatory T cells

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