CD45 is required for type I IFN production by dendritic cells

CD45 is a leukocyte tyrosine phosphatase, essential for normal immune responses. We have studied the function of splenic dendritic cells of CD45+/+, CD45–/–, CD45RABC and CD45RO transgenic mice. We show that there are increased numbers of plasmacytoid dendritic cells in CD45–/– mice. DC of all mice are capable of responding to lymphocytic choriomeningitis virus (LCMV) infection by up‐regulation of MHC and costimulatory molecules. DC of CD45–/– mice have an impaired capacity to produce type I interferons in response to LCMV infection in vivo. These data indicate that lack of CD45 expression in DC has a profound effect on their function. This is largely restored by CD45RABC or CD45RO transgenes.

[1]  S. Petrova,et al.  CD45 negatively regulates tumour necrosis factor and interleukin‐6 production in dendritic cells , 2006, Immunology.

[2]  D. Levy,et al.  Tissue-specific Positive Feedback Requirements for Production of Type I Interferon following Virus Infection* , 2005, Journal of Biological Chemistry.

[3]  P. Borrow,et al.  Rapid Activation of Spleen Dendritic Cell Subsets following Lymphocytic Choriomeningitis Virus Infection of Mice: Analysis of the Involvement of Type 1 IFN1 , 2005, The Journal of Immunology.

[4]  W. Bodmer,et al.  Disease associations and altered immune function in CD45 138G variant carriers. , 2004, Human molecular genetics.

[5]  P. Borrow,et al.  Altered CD45 isoform expression affects lymphocyte function in CD45 Tg mice. , 2004, International immunology.

[6]  K. Tyler,et al.  Does Toll-like receptor 3 play a biological role in virus infections? , 2004, Virology.

[7]  P. Kaleebu,et al.  CD45 variant alleles: possibly increased frequency of a novel exon 4 CD45 polymorphism in HIV seropositive Ugandans , 2004, Immunogenetics.

[8]  M. Hermiston,et al.  CD45: a critical regulator of signaling thresholds in immune cells. , 2003, Annual review of immunology.

[9]  P. Borrow,et al.  Cross-priming of CD8+ T cells stimulated by virus-induced type I interferon , 2003, Nature Immunology.

[10]  K. Toellner,et al.  Extrafollicular antibody responses , 2003, Immunological reviews.

[11]  T. Wirth,et al.  Bruton's Tyrosine Kinase Is a Toll/Interleukin-1 Receptor Domain-binding Protein That Participates in Nuclear Factor κB Activation by Toll-like Receptor 4* , 2003, Journal of Biological Chemistry.

[12]  D. Levy,et al.  Central role for type I interferons and Tyk2 in lipopolysaccharide-induced endotoxin shock , 2003, Nature Immunology.

[13]  S. Ehlers,et al.  Enhanced frequency of a PTPRC (CD45) exon A mutation (77C→G) in systemic sclerosis , 2003, Genes and Immunity.

[14]  Li Wu,et al.  Mouse Plasmacytoid Cells , 2002, The Journal of experimental medicine.

[15]  C. Biron,et al.  Promotion of Alpha/Beta Interferon Induction during In Vivo Viral Infection through Alpha/Beta Interferon Receptor/STAT1 System-Dependent and -Independent Pathways , 2002, Journal of Virology.

[16]  A. Ziegler,et al.  A novel mutation in PTPRC interferes with splicing and alters the structure of the human CD45 molecule , 2002, Immunogenetics.

[17]  G. Trinchieri,et al.  Interferon / and Interleukin 12 Responses to Viral Infections: Pathways Regulating Dendritic Cell Cytokine Expression In Vivo , 2002 .

[18]  E. Tchilian,et al.  A point mutation in CD45 may be associated with an increased risk of HIV-1 infection. , 2001, AIDS.

[19]  Josef M. Penninger,et al.  CD45: new jobs for an old acquaintance , 2001, Nature Immunology.

[20]  Josef M. Penninger,et al.  CD45 is a JAK phosphatase and negatively regulates cytokine receptor signalling , 2001, Nature.

[21]  M. Bevan,et al.  Cd8+ but Not Cd8− Dendritic Cells Cross-Prime Cytotoxic T Cells in Vivo , 2000, The Journal of experimental medicine.

[22]  D. Flynn,et al.  Effects of the protein tyrosine phosphatase CD45 on FcgammaRIIa signaling and neutrophil function. , 2000, Experimental hematology.

[23]  M. Bachmann,et al.  CTL priming by CD8+ and CD8– dendritic cells in vivo , 1999, European journal of immunology.

[24]  R. Steinman,et al.  Dendritic cells and the control of immunity , 1998, Nature.

[25]  J. Altman,et al.  Counting antigen-specific CD8 T cells: a reevaluation of bystander activation during viral infection. , 1998, Immunity.

[26]  T. Roach,et al.  CD45 regulates Src family member kinase activity associated with macrophage integrin-mediated adhesion , 1997, Current Biology.

[27]  Y. Kong,et al.  Enhanced generation of NK cells with intact cytotoxic function in CD45 exon 6-deficient mice. , 1996, Journal of immunology.

[28]  D. Alexander,et al.  CD45-null transgenic mice reveal a positive regulatory role for CD45 in early thymocyte development, in the selection of CD4+CD8+ thymocytes, and B cell maturation , 1996, The Journal of experimental medicine.

[29]  A. Chong,et al.  CD45-cross-linking stimulates IFN-gamma production in NK cells. , 1995, Journal of immunology.

[30]  T. Mak,et al.  Leukocyte common antigen (CD45) is required for immunoglobulin E- mediated degranulation of mast cells , 1994, The Journal of experimental medicine.

[31]  M Aguet,et al.  Functional role of type I and type II interferons in antiviral defense. , 1994, Science.

[32]  Li Wu,et al.  The surface phenotype of dendritic cells purified from mouse thymus and spleen: investigation of the CD8 expression by a subpopulation of dendritic cells , 1992, The Journal of experimental medicine.

[33]  R. Zinkernagel,et al.  Immune response against lymphocytic choriomeningitis virus infection in mice without CD8 expression , 1991, The Journal of experimental medicine.

[34]  L. Terry,et al.  Limiting dilution analysis of proliferative responses in human lymphocyte populations defined by the monoclonal antibody UCHL1: implications for differential CD45 expression in T cell memory formation , 1988, European journal of immunology.

[35]  G. Janossy,et al.  Loss of CD45R and gain of UCHL1 reactivity is a feature of primed T cells. , 1988, Journal of immunology.

[36]  D. Moskophidis,et al.  Mechanism of recovery from acute virus infection: treatment of lymphocytic choriomeningitis virus-infected mice with monoclonal antibodies reveals that Lyt-2+ T lymphocytes mediate clearance of virus and regulate the antiviral antibody response , 1987, Journal of virology.

[37]  M. Oldstone,et al.  Genomic and biological variation among commonly used lymphocytic choriomeningitis virus strains. , 1983, The Journal of general virology.

[38]  P. Borrow,et al.  Altered CD 45 isoform expression affects lymphocyte function in CD 45 Tg mice , 2004 .

[39]  M. Manns,et al.  77 C/G mutation in the tyrosine phosphatase CD45 gene and autoimmune hepatitis: evidence for a genetic link , 2003, Genes and Immunity.

[40]  T. Wirth,et al.  Bruton's tyrosine kinase is a Toll/interleukin-1 receptor domain-binding protein that participates in nuclear factor kappaB activation by Toll-like receptor 4. , 2003, The Journal of biological chemistry.

[41]  Li Wu,et al.  Mouse Plasmacytoid Cells: Long-lived Cells, Heterogeneous in Surface Phenotype and Function, that Differentiate Into CD8 (cid:2) Dendritic Cells Only after Microbial Stimulus , 2002 .

[42]  G. Trinchieri,et al.  Interferon alpha/beta and interleukin 12 responses to viral infections: pathways regulating dendritic cell cytokine expression in vivo. , 2002, The Journal of experimental medicine.

[43]  E. Petricoin,et al.  Antiproliferative action of interferon-alpha requires components of T-cell-receptor signalling. , 1997, Nature.