Disease relevance of LRRC23

• Because of our interest in the immunologic basis of benign and malignant T-cell-mediated disorders of the skin, we investigated the cellular distribution of CD28 and B7 family members in lesions of psoriasis and mycosis fungoides [1].
• Expression of the co-stimulatory molecule B7 on melanoma cells [2].
• In this study, we have investigated the relationship between the regulation of B7 isoform expression on antigen-presenting cells from HIV+ individuals and the production of Th cytokines [3].
• We speculate that "alternative" T cell-activation via the B7/CD28 pathway may contribute to the pathogenesis of these skin diseases [4].
• No B7/BB1 immunoreactivity was detected in normal skin and basal cell carcinoma [4].

High impact information on LRRC23

• Recent studies suggest that interaction of CD28 with B7 on APC might deliver such a costimulatory signal [5].
• Stimulation of T cells with B7+ CHO cells also specifically increased levels of interleukin 2 transcripts [6].
• Immobilized B7 Ig and B7+ CHO cells costimulated T cell proliferation [6].
• Cellular interactions mediated by B7 and CD28 may represent an important component of the functional interactions between T and B lymphoid cells [6].
• Blockade of B7/CD28 in mixed lymphocyte reaction cultures results in the generation of alternatively activated macrophages, which suppress T-cell responses [7].

Biological context of LRRC23

• To investigate the role of CD28 signal transduction during APC-dependent T cell activation, we have used Staphylococcal enterotoxins (SEs) presented by a B7-positive APC [5].
• Following warming to 37 degrees C, cLC tagged with anti-B7 monoclonal antibody and gold-conjugated secondary antibody could internalize surface B7 by using the organelles of receptor-mediated endocytosis [8].
• Interactions of CD28 (on T cells) with its recently identified ligand B7/BB1 (on antigen-presenting cells) have been shown to activate T cells via a major histocompatibility complex/Ag-independent "alternative" pathway, leading to an amplification of T-cell-mediated immune responses [4].
• These findings indicate that T-cell-mediated skin diseases are accompanied by an influx of CD28+ T cells and an upregulation of B7/BB1 on cutaneous antigen-presenting cells, keratinocytes, and on some T cells [4].
• Notably, simultaneous blockade of the CD28/B7 pathway did not further augment graft survival but did suppress the development of donor-specific antibodies, an effect not achieved with Chi220 alone, despite peripheral B cell depletion [9].

Anatomical context of LRRC23

• Furthermore, keratinocytes bind specifically to CD28-transfected COS7 cells, and this binding is inhibited by anti-CD28 and anti-BB-1 but not B7 MAbs [10].
• These studies suggest: 1) that the MAb against BB-1 binds a functional epitope on a molecule distinct from B7 as detected on activated keratinocytes in vitro and in vivo and 2) that keratinocytes in skin and epithelial cells in thymus can express cell-surface molecules that might mediate T-cell co-stimulation via CD28 [10].
• Our results indicate that although mRNA for B7 is present in 40-50% of melanoma cell lines, expression at the protein level is at low or undetectable levels in the majority of the cell lines [2].
• B7 molecule on CLC may be relevant to their increased antigen-presenting cell potency and ability to stimulate naive T lymphocytes [8].
• Expression of B7 costimulatory molecule in cultured human epidermal Langerhans cells is regulated at the mRNA level [8].

Associations of LRRC23 with chemical compounds

• Expression and localization of leucine-rich B7 protein in human ocular tissues [11].
• The modified gene, gsB7, transfected into J27.2 or C1R cell lines, produced a secreted protein, sB7, serologically recognized as B7 [12].

Regulatory relationships of LRRC23

• These BB-1 positive cells fail to express detectable B7 messenger RNA by Northern blot analysis [10].

Other interactions of LRRC23

• In this study, we evaluated the expression of B7 costimulatory molecule (CD80) in human freshly isolated (fLC) and cLC at both the protein and mRNA level [8].
• Analysis of B7 expression by flow cytometry using the BB1 MAb revealed low levels of expression in 3 of 10 melanoma that had mRNA for B7 [2].
• B7 mRNA, detected by the reverse-transcriptase polymerase chain reaction technique, was expressed at a low level in purified (> 90% HLA-DR+) fLC but not in LC-depleted epidermal cells, and was markedly upregulated in purified cLC [8].

Analytical, diagnostic and therapeutic context of LRRC23

• In contrast to lymphocyte function-associated Ag-1/intercellular adhesion molecule-1, CD28/B7 interaction was not required for anti-CD2-induced proliferation, although ligation of these molecules provided important costimulatory signals for stimulation by anti-CD3 [13].
• In the present study the expression of B7 on cultured human melanoma cells was studied at the mRNA level by reverse PCR analysis and surface expression by flow cytometric analysis with monoclonal antibodies (MAbs) [2].
• Staining of frozen skin sections did not reveal any epidermal dendritic cell reactive with either of two different anti-B7 monoclonal antibodies. fLC in suspension did not exhibit any B7 staining as evaluated by two-color flow-cytometry analysis and immunoelectron microscopy [8].
• This study shows that blockade of B7/CD28 in anergizing mixed lymphocyte reaction (MLR) cultures of peripheral blood mononuclear cells results in the generation of alternatively activated macrophages (AAMphi) [7].
• Blockade of B7/CD28 costimulation allows human haploidentical bone marrow transplantation without graft-versus-host disease [7].

References