A Possible Pathogenic Role of CD8
            <sup>+</sup>
            T Cells and their Derived Cytokine, IL-16, in SLE

Sekigawa, Iwao; Matsushita, Masakazu; Lee, Shouseki; Maeda, Nobuki; Ogasawara, Hitoshi; Kaneko, Hiroshi; Iida, Noboru; Hashimoto, Hiroshi

doi:10.3109/08916930108994108

Cited by 26 publications

(23 citation statements)

References 52 publications

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“…25 Exogenous and endogenous antigens are recognised by CD4 þ or CD8 þ T cells, respectively. In SLE, a decrease in the CD4/CD8 ratio can be observed that is due to an increase in the numbers of CD8 þ cells, [26][27][28] whereas for atopic dermatitis an increase in the CD4/CD8 ratio results from the expansion of CD4 þ cells. 29 It seems likely that the coexistence of two diseases dependent on differences in the CD4/CD8 ratio will be rare because the presence of one type of disease reduces the likelihood that the other develops.…”

Section: Discussionmentioning

confidence: 99%

PDCD1: a tissue-specific susceptibility locus for inherited inflammatory disorders

et al. 2005

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Variation in genes encoding costimulatory molecules expressed on lymphocytes has been expected to contribute to the genetic component of inflammatory disease, but only the gene encoding the inhibitory protein, CTLA-4, seems consistently to confer disease susceptibility. Studies in murine models implicate the inhibitory product of the pd1 gene, programmed death-1, in the maintenance of peripheral tolerance to self-antigens. We identify 22 single-nucleotide polymorphisms (SNPs) in the equivalent human gene, PDCD1, a number of which show significant associations with the specific immunoglobulin E response to grass allergens in atopic individuals. Stepwise analyses indicate that four of the disease-associated SNPs have independent effects. The two most common haplotypes show positive and negative associations but rarer haplotypes are also likely to be of influence. In a case-control study, multiple regression analysis of genotypic data implies that PDCD1 also confers susceptibility to rheumatoid arthritis. Along with work linking PDCD1 with susceptibility to another autoimmune condition, systemic lupus erythematosus, our data identify PDCD1 as a second immunomodulatory gene with pleiotropic effects in human disease. Genes encoding negative regulators may generally confer a significant fraction of the genetic risk associated with inherited inflammatory disorders.

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Section: Discussionmentioning

confidence: 99%

PDCD1: a tissue-specific susceptibility locus for inherited inflammatory disorders

et al. 2005

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“…6 Autoantibodies against nuclear antigens are found in virtually all patients with SLE, and these antibodies show evidence for somatic hypermutation, indicating the involvement of CD4 T cells. Lupus is also characterized by widespread dysregulation of CD8 T cells and myeloid lineage cells, [7][8][9] and knockout mice for a variety of immune system genes, including many involved in negative regulation of lymphoid signaling, develop lupus-like disease. 10,11 The MRLlpr mouse strain is one of the best-studied models for spontaneous lupus.…”

Section: Introductionmentioning

confidence: 99%

Genomic view of systemic autoimmunity in MRLlpr mice

et al. 2006

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MRLlpr mice develop spontaneous systemic autoimmunity with many hallmarks of the human disease systemic lupus erythematosus. Although a variety of genes have been implicated in this model, disease pathogenesis is still poorly understood. In an effort to identify novel genes and pathways, we performed genome-wide mRNA expression analysis in the spleens and kidneys of MRLlpr mice throughout the disease course. Samples were collected from cohorts of C57BL/6, MRL þ / þ and MRLlpr mice, and profiled by flow cytometry and gene expression microarrays. Serum autoantibodies and renal pathology were studied in parallel. We identified 236 genes in MRLlpr spleen that showed significant threefold or greater changes in expression between 6 and 20 weeks. Of interest, a number of interferon-responsive genes were expressed early, and remained dysregulated throughout the disease course. Many chemokines, cell surface proteins, transcription factors and cytokines, including IFN-gamma, also showed altered expression as disease progressed. Analysis of kidneys indicated the presence of severe inflammation that coincided with evidence for changes in kidney function and elevated expression of IFNinducible genes, complement components and antigen presentation genes. These data provide a unique genomic view of the progression to fatal autoimmunity in MRLlpr mice, and provide new candidate genes and pathways to explore.

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“…IL-16 is a CD8+T cell-derived cytokine that uses CD4 as its receptor (52) and can inhibit HIV-1 infection in vitro (53). This cytokine also induces activation and anergy of CD4+ T cells observed in SLE (52,54,55). Although several possibilities have been proposed, we think that IL-16 may have a protective effect against HIV infection in SLE patients and maycontribute to the low incidence of the coexistence of both diseases (50).…”

Section: Hiv and Autoimmunitymentioning

confidence: 99%

“…Our recent studies have indicated that synthetic clone 4-1-derived pl5E peptides can induce CD4+ T cell activation and anergy, production of several cytokines (including IL-1 6), and cytokine-related PBAin vitro (data not shown). Such CD4+ T cell abnormalities may contribute to the loss of self-tolerance and the induction of SLE-related autoimmune phenomena (including autoantibody production) in cooperation with PBA(62) and in addition to the role of molecular mimicry between certain retroviral components and autoantibodies, which is also reported to be important for autoantibody development and with the rise in the serum level ofIL-16 (55,65). Also, the removal of activated CD8+T cells and the loss of factors produced by these cells normalizes CD4+T cell abnormalities such as decreased in vitro IL-2 production in SLE (66,67).…”

Section: ) (58)mentioning

confidence: 99%

“…Also, the removal of activated CD8+T cells and the loss of factors produced by these cells normalizes CD4+T cell abnormalities such as decreased in vitro IL-2 production in SLE (66,67). Thus, activated CD8+T cells and/or the cytokines derived from these cells seem to influence both the decrease of CD4+T cell numbers and the impairment of CD4+T cell function in SLE (55). In general, endogenous antigens such as HERVare presented with HLAclass I molecules and are recognized by CD8+T cells (68).…”

Section: ) (58)mentioning

confidence: 99%

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Retroviruses and Autoimmunity.

et al. 2001

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The investigation of humanretroviruses has showndramatic progress since the discovery of human immunodeficiency virus (HIV). These studies have also contributed to the exploration of the role of retroviruses, including endogenous retroviruses, in the induction of autoimmune diseases such as systemic lupus erythematosus (SLE). This review describes the potential role of retroviruses in autoimmunity, based on recent findings including our own results. (Internal Medicine 40: 80-86, 2001)

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A Possible Pathogenic Role of CD8 ⁺ T Cells and their Derived Cytokine, IL-16, in SLE

Cited by 26 publications

References 52 publications

PDCD1: a tissue-specific susceptibility locus for inherited inflammatory disorders

PDCD1: a tissue-specific susceptibility locus for inherited inflammatory disorders

Genomic view of systemic autoimmunity in MRLlpr mice

Retroviruses and Autoimmunity.

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A Possible Pathogenic Role of CD8 + T Cells and their Derived Cytokine, IL-16, in SLE

Cited by 26 publications

References 52 publications

PDCD1: a tissue-specific susceptibility locus for inherited inflammatory disorders

PDCD1: a tissue-specific susceptibility locus for inherited inflammatory disorders

Genomic view of systemic autoimmunity in MRLlpr mice

Retroviruses and Autoimmunity.

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Product

Resources

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A Possible Pathogenic Role of CD8 ⁺ T Cells and their Derived Cytokine, IL-16, in SLE