Inhibitory Receptors CD85j, LAIR-1, and CD152 Down-Regulate Immunoglobulin and Cytokine Production by Human B Lymphocytes

Merlo, Andrea; Tenca, Claudya; Fais, Franco; Battini, Lorenzo; Ciccone, Ermanno; Grossi, Carlo E.; Saverino, Danièle

doi:10.1128/cdli.12.6.705-712.2005

Cited by 78 publications

(73 citation statements)

References 34 publications

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“…IFN-␥ and IFN-␣ responses were diminished when PBMC or purified T cells were cocultured with fibroblasts infected with UL18 deletion virus compared with the parental strain AD169, a rather surprising finding considering the inhibitory functions of the UL18R LIR-1 (25,27,31,47,48). Other studies using dUL18 virus to detect a potential inhibitory effect of UL18 on NK cells also observe rather an enhancement of killing instead of inhibition (22,23).…”

Section: Discussionmentioning

confidence: 84%

Increased Expression of Leukocyte Ig-Like Receptor-1 and Activating Role of UL18 in the Response to Cytomegalovirus Infection

Wagner

Riise²,

Bergström

et al. 2007

The Journal of Immunology

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NK and T cells are important for combating CMV infection. Some NK and T cells express leukocyte Ig-like receptor-1 (LIR-1), an inhibitory receptor recognizing MHC class I and the CMV-encoded homolog UL18. We previously demonstrated an early increase in LIR-1-expressing blood lymphocytes in lung-transplanted patients later developing CMV disease. We now show that NK and T cells account for the observed LIR-1 augmentation. Coincubation of PBMC from CMV-seropositive donors with virus-infected lung fibroblasts led to a T cell-dependent secretion of IFN-γ, produced mainly by LIR-1+ T cells and by NK cells. Cytokine production during coculture with fibroblasts infected with virus containing the UL18 gene was augmented compared with the UL18 deletion virus, suggesting a stimulatory role for UL18. However, purified UL18Fc proteins inhibited IFN-γ production of LIR-1+ T cells. We propose that cytokine production in the transplant induces NK and T cells to express LIR-1, which may predispose to CMV disease by MHC/LIR-1-mediated suppression. Although the UL18/LIR-1 interaction could inhibit T cell responses, this unlikely plays a role in response to infected cells. Instead, our data point to an activating role for viral UL18 during infection, where indirect intracellular effects cannot be excluded.

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Section: Discussionmentioning

confidence: 84%

Increased Expression of Leukocyte Ig-Like Receptor-1 and Activating Role of UL18 in the Response to Cytomegalovirus Infection

Wagner

Riise²,

Bergström

et al. 2007

The Journal of Immunology

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“…In contrast, cytotoxic T-lymphocyte antigen-4 (CTLA-4, CD152), a homologue to CD28, is a T-cell costimulatory receptor able to attenuate the immune response [4][5][6]. CTLA-4 is expressed on activated T cells (both CD4 + and CD8 + ) and B cells [7] and on monocytes and dendritic cells [8], and acts to downregulate cell functions. In addition, CTLA-4 is expressed on the surface of regulatory T cells, acting largely as a negative regulator of T cell responses [9].…”

Section: Introductionmentioning

confidence: 99%

The soluble CTLA-4 receptor and its role in autoimmune diseases: an update

Saverino

Simone

Bagnasco

et al. 2010

Autoimmun Highlights

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CTLA-4, initially described as a membranebound molecule, is a costimulatory receptor transducing a potent inhibitory signal. Increasing evidence shows the CTLA-4 gene to be an important susceptibility locus for autoimmune endocrinopathies and other autoimmune disorders. A soluble form of cytotoxic T-lymphocyte-associated antigen-4 (sCTLA-4) has been established and shown to possess CD80/CD86 binding activity and in vitro immunoregulatory functions. sCTLA-4 is generated by alternatively spliced mRNA. Whereas low levels of sCTLA-4 are detected in normal human serum, increased serum levels are observed in several autoimmune diseases (e.g. Graves’ disease, myasthenia gravis, systemic lupus erythematosus, type 1 diabetes, systemic sclerosis, coeliac disease, autoimmune pancreatitis and primary biliary cirrhosis). The biological significance of increased sCTLA-4 serum levels is not fully clarified yet. On the one hand, it can be envisaged that sCTLA-4 specifically inhibits early T-cell activation by blocking the interaction of CD80/CD86 with the costimulatory receptor CD28. On the other hand, higher levels of sCTLA-4 could compete for the binding of the membrane form of CTLA-4 with CD80/CD86 in the later phases of T-lymphocyte activation, causing a reduction in inhibitory signalling. This double-edged nature of sCTLA-4 to block the binding of CD28 to CD80/CD86 may result in different outcomes during the clinical course of an autoimmune disease.

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“…There are suggestive data claiming that CTLA-4 might influence isotype class switching to IgG1 and IgE in vitro (25,45). Ϫ/Ϫ B cell chimeric mice as compared with C57BL/6 B cell chimeric mice, respectively (Fig.…”

Section: Normal B and T Cell Homeostasis And Development In Mice Withmentioning

confidence: 99%

A New Role of CTLA-4 on B Cells in Thymus-Dependent Immune Responses In Vivo

Quandt

Hoff

Rudolph

et al. 2007

The Journal of Immunology

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The expression of CTLA-4 (CD152) on the cell surface of B cells and its consequences for the humoral immune response in vivo are unknown. We investigated the expression of CTLA-4 mRNA and protein in B cells in T cell-independent or -dependent ways. B cells in the presence of Ag-stimulated Th2 cells expressed mRNA of CTLA-4 and up-regulated intracellular CTLA-4 protein. Using a liposome-enhanced staining technique, we show for the first time, that surface CTLA-4 protein is expressed by 11–15% of B cells in a T cell-dependent culture system. To dissect the role of CTLA-4 on B cells in vivo, we used bone marrow chimeric mice in which only B cells were CTLA-4 deficient. These mice showed that early B cell development and homeostasis is not influenced by CTLA-4 deficiency of B cells. Ag-specific responses after immunization of the chimeric mice revealed elevated levels of IgM Abs in mice deficient for B cell CTLA-4. We propose that CTLA-4 signals on B cells determine the early fate of B cells in thymus-dependent immune responses.

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Inhibitory Receptors CD85j, LAIR-1, and CD152 Down-Regulate Immunoglobulin and Cytokine Production by Human B Lymphocytes

Cited by 78 publications

References 34 publications

Increased Expression of Leukocyte Ig-Like Receptor-1 and Activating Role of UL18 in the Response to Cytomegalovirus Infection

Increased Expression of Leukocyte Ig-Like Receptor-1 and Activating Role of UL18 in the Response to Cytomegalovirus Infection

The soluble CTLA-4 receptor and its role in autoimmune diseases: an update

A New Role of CTLA-4 on B Cells in Thymus-Dependent Immune Responses In Vivo

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