{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T09:02:59Z","timestamp":1790326979409,"version":"4.1.0"},"reference-count":68,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2009,9,1]],"date-time":"2009-09-01T00:00:00Z","timestamp":1251763200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>It is known that C3 is required for optimal expansion of T cells during acute viral infections. However, it is not yet determined whether T cell responses to intracellular bacterial infections require C3. Therefore, we have investigated the requirement for C3 to elicit potent T cell responses to Listeria monocytogenes (LM). We show that expansion of Ag-specific CD8 and CD4 T cells during a primary response to LM was markedly reduced in the absence of C3 activity. Further studies indicated that, unlike in an influenza virus infection, the regulation of LM-specific T cell responses by C3 might not involve the downstream effector C5a. Moreover, reduced T cell responses to LM was not linked to defective maturation of dendritic cells or developmental anomalies in the peripheral T cell compartment of C3-deficient mice. Experiments involving adoptive transfer of C3-deficient CD8 T cells into the C3-sufficient environment of wild-type mice showed that these T cells do not have intrinsic proliferative defects, and a paracrine source of C3 will suffice for clonal expansion of CD8 T cells in vivo. However, stimulation of purified C3-deficient CD8 T cells by plastic-immobilized anti-CD3 showed that C3 promotes T cell proliferation directly, independent of its effects on APC. On the basis of these findings, we propose that diminished T cell responses to LM in C3-deficient mice might be at least in part due to lack of direct effects of C3 on T cells. These studies have furthered our understanding of C3-mediated regulation of T cell immunity to intracellular pathogens.<\/jats:p>","DOI":"10.4049\/jimmunol.0801191","type":"journal-article","created":{"date-parts":[[2009,7,31]],"date-time":"2009-07-31T21:10:19Z","timestamp":1249074619000},"page":"2921-2931","source":"Crossref","is-referenced-by-count":38,"title":["C3 Promotes Expansion of CD8+ and CD4+ T Cells in a\n                    <i>Listeria monocytogenes<\/i>\n                    Infection"],"prefix":"10.1093","volume":"183","author":[{"given":"Yumi","family":"Nakayama","sequence":"first","affiliation":[{"name":"Department of Pathobiological Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin-Il","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Wisconsin , Madison, WI 53706"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eui Ho","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pathobiological Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John D","family":"Lambris","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Pennsylvania , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matyas","family":"Sandor","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Wisconsin , Madison, WI 53706"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Suresh","sequence":"additional","affiliation":[{"name":"Department of Pathobiological Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,9,1]]},"reference":[{"key":"2026012811255411100_R1","first-page":"132","article-title":"Complement evasion by human pathogens.","volume-title":"Nat. Rev. Microbiol.","year":"2008"},{"key":"2026012811255411100_R2","first-page":"715","article-title":"The role of complement in inflammatory diseases from behind the scenes into the spotlight.","volume-title":"Am. J. Pathol.","year":"2007"},{"key":"2026012811255411100_R3","first-page":"64","article-title":"Complement and the immune response.","volume-title":"Curr. Opin. Immunol.","year":"1997"},{"key":"2026012811255411100_R4","first-page":"36","article-title":"Linkages of innate and adaptive immunity.","volume-title":"Curr. Opin. Immunol.","year":"1998"},{"key":"2026012811255411100_R5","first-page":"127","article-title":"The CD19\/CR2\/TAPA-1 complex of B lymphocytes: linking natural to acquired immunity.","volume-title":"Annu. Rev. Immunol.","year":"1995"},{"key":"2026012811255411100_R6","first-page":"397","article-title":"Complement deficiency and immune complex disease.","volume-title":"Springer Semin. Immunopathol.","year":"1994"},{"key":"2026012811255411100_R7","first-page":"227","article-title":"Systemic lupus erythematosus, complement deficiency, and apoptosis.","volume-title":"Adv. Immunol.","year":"2000"},{"key":"2026012811255411100_R8","first-page":"1140","article-title":"Complement: second of two parts.","volume-title":"N. Engl. J. Med.","year":"2001"},{"key":"2026012811255411100_R9","first-page":"103","article-title":"The role of the complement system in innate immunity.","volume-title":"Immunol. Res.","year":"2005"},{"key":"2026012811255411100_R10","first-page":"373","article-title":"Complement component C3 promotes T cell priming and lung migration to control acute influenza virus infection.","volume-title":"Nat. Med.","year":"2002"},{"key":"2026012811255411100_R11","first-page":"788","article-title":"Complement component 3 is required for optimal expansion of CD8 T cells during a systemic viral infection.","volume-title":"J. Immunol.","year":"2003"},{"key":"2026012811255411100_R12","first-page":"2524","article-title":"Complement C5a receptor is essential for the optimal generation of antiviral CD8+ T cell responses.","volume-title":"J. Immunol.","year":"2004"},{"key":"2026012811255411100_R13","first-page":"1287","article-title":"Natural antibodies and complement are endogenous adjuvants for vaccine-induced CD8+ T cell responses.","volume-title":"Nat. Med.","year":"2003"},{"key":"2026012811255411100_R14","first-page":"582","article-title":"Local synthesis of complement component C3 regulates acute renal transplant rejection.","volume-title":"Nat. Med.","year":"2002"},{"key":"2026012811255411100_R15","first-page":"812","article-title":"Immune responses to Listeria monocytogenes.","volume-title":"Nat. Rev. Immunol.","year":"2004"},{"key":"2026012811255411100_R16","first-page":"107","article-title":"The cytokine stew and innate resistance to L. monocytogenes.","volume-title":"Immunol. Rev.","year":"1997"},{"key":"2026012811255411100_R17","first-page":"3116","article-title":"Studies with MHC-deficient knockout mice reveal impact of both MHC I- and MHC II-dependent T cell responses on Listeria monocytogenes infection.","volume-title":"J. Immunol.","year":"1994"},{"key":"2026012811255411100_R18","first-page":"11","article-title":"Studies in listeriosis show the strong symbiosis between the innate cellular system and the T cell response.","volume-title":"Immunol. Rev.","year":"1997"},{"key":"2026012811255411100_R19","first-page":"35","article-title":"Interrelationship among macrophages, natural killer cells and neutrophils in early stages of Listeria resistance.","volume-title":"Curr. Opin. Immunol.","year":"1997"},{"key":"2026012811255411100_R20","first-page":"109","article-title":"Specific immunity to Listeria monocytogenes in the absence of IFN-\u03b3.","volume-title":"Immunity","year":"1995"},{"key":"2026012811255411100_R21","first-page":"457","article-title":"Mice deficient for the 55 kd tumor necrosis factor receptor are resistant to endotoxic shock, yet succumb to L. monocytogenes infection.","volume-title":"Cell","year":"1993"},{"key":"2026012811255411100_R22","first-page":"798","article-title":"Mice lacking the tumour necrosis factor receptor 1 are resistant to TNF-mediated toxicity but highly susceptible to infection by Listeria monocytogenes.","volume-title":"Nature","year":"1993"},{"key":"2026012811255411100_R23","first-page":"1742","article-title":"Immune response in mice that lack the interferon \u03b3 receptor.","volume-title":"Science","year":"1993"},{"key":"2026012811255411100_R24","first-page":"1","article-title":"Complement receptor type 3 mediates phagocytosis and killing of Listeria monocytogenes by a TNF-\u03b1- and IFN-\u03b3-stimulated macrophage precursor hybrid.","volume-title":"Cell. Immunol.","year":"1996"},{"key":"2026012811255411100_R25","first-page":"2786","article-title":"An anti-CD3 monoclonal antibody protects mice against a lethal infection with Listeria monocytogenes through induction of endogenous cytokines.","volume-title":"Infect. Immun.","year":"1993"},{"key":"2026012811255411100_R26","first-page":"2645","article-title":"Roles of complement and complement receptor type 3 in phagocytosis of Listeria monocytogenes by inflammatory mouse peritoneal macrophages.","volume-title":"Infect. Immun.","year":"1991"},{"key":"2026012811255411100_R27","first-page":"5431","article-title":"Complement receptor type 3 (CD11b\/CD18) involvement is essential for killing of Listeria monocytogenes by mouse macrophages.","volume-title":"J. Immunol.","year":"1993"},{"key":"2026012811255411100_R28","first-page":"135","article-title":"Genetic disruption of the murine complement C3 promoter region generates deficient mice with extrahepatic expression of C3 mRNA.","volume-title":"Immunopharmacology","year":"1999"},{"key":"2026012811255411100_R29","first-page":"86","article-title":"The C5a chemoattractant receptor mediates mucosal defence to infection.","volume-title":"Nature","year":"1996"},{"key":"2026012811255411100_R30","first-page":"2053","article-title":"Role of CD4 T cell help and costimulation in CD8 T cell responses during Listeria monocytogenes infection.","volume-title":"J. Immunol.","year":"2003"},{"key":"2026012811255411100_R31","first-page":"1693","article-title":"Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte\/macrophage colony-stimulating factor.","volume-title":"J. Exp. 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Chem.","year":"1999"},{"key":"2026012811255411100_R35","first-page":"177","article-title":"Counting antigen-specific CD8 T cells: a reevaluation of bystander activation during viral infection.","volume-title":"Immunity","year":"1998"},{"key":"2026012811255411100_R36","first-page":"459","article-title":"CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation.","volume-title":"J. Exp. Med.","year":"1995"},{"key":"2026012811255411100_R37","first-page":"45","article-title":"T cell responses to Listeria monocytogenes.","volume-title":"Curr. Opin. Microbiol.","year":"2004"},{"key":"2026012811255411100_R38","first-page":"821","article-title":"Role of C5a in inflammatory responses.","volume-title":"Annu. Rev. Immunol.","year":"2005"},{"key":"2026012811255411100_R39","first-page":"1058","article-title":"Complement: first of two parts.","volume-title":"N. Engl. J. Med.","year":"2001"},{"key":"2026012811255411100_R40","first-page":"2631","article-title":"Anaphylatoxin C5a induces monocyte recruitment and differentiation into dendritic cells by TNF-\u03b1 and prostaglandin E2-dependent mechanisms.","volume-title":"J. Immunol.","year":"2003"},{"key":"2026012811255411100_R41","first-page":"425","article-title":"Locally produced complement fragments C5a and C3a provide both costimulatory and survival signals to naive CD4+ T cells.","volume-title":"Immunity","year":"2008"},{"key":"2026012811255411100_R42","first-page":"56","article-title":"Expression of EBV\/C3d receptors on T cells: biological significance.","volume-title":"Immunol. Today","year":"1993"},{"key":"2026012811255411100_R43","first-page":"3292","article-title":"Migration of dendritic cells in response to formyl peptides, C5a, and a distinct set of chemokines.","volume-title":"J. Immunol.","year":"1995"},{"key":"2026012811255411100_R44","first-page":"388","article-title":"Activation of human CD4+ cells with CD3 and CD46 induces a T-regulatory cell 1 phenotype.","volume-title":"Nature","year":"2003"},{"key":"2026012811255411100_R45","first-page":"102","article-title":"Holding T cells in check\u2014a new role for complement regulators?.","volume-title":"Trends Immunol.","year":"2006"},{"key":"2026012811255411100_R46","first-page":"171","article-title":"Complement: central to innate immunity and bridging to adaptive responses.","volume-title":"Immunol. Lett.","year":"2005"},{"key":"2026012811255411100_R47","first-page":"3330","article-title":"Dendritic cell synthesis of C3 is required for full T cell activation and development of a Th1 phenotype.","volume-title":"J. Immunol.","year":"2006"},{"key":"2026012811255411100_R48","first-page":"2461","article-title":"Macrophages from C3-deficient mice have impaired potency to stimulate alloreactive T cells.","volume-title":"Blood","year":"2006"},{"key":"2026012811255411100_R49","first-page":"1397","article-title":"Differential susceptibility of bone marrow-derived dendritic cells and macrophages to productive infection with Listeria monocytogenes.","volume-title":"Cell. Microbiol.","year":"2007"},{"key":"2026012811255411100_R50","first-page":"1265","article-title":"Complement-targeted therapeutics.","volume-title":"Nat. Biotechnol.","year":"2007"},{"key":"2026012811255411100_R51","first-page":"5363","article-title":"Myeloid C3 determines induction of humoral responses to peripheral herpes simplex virus infection.","volume-title":"J. Immunol.","year":"2003"},{"key":"2026012811255411100_R52","first-page":"1861","article-title":"Cellular expression of the C5a anaphylatoxin receptor (C5aR): demonstration of C5aR on nonmyeloid cells of the liver and lung.","volume-title":"J. Immunol.","year":"1995"},{"key":"2026012811255411100_R53","first-page":"469","article-title":"Functions of anaphylatoxin C5a in rat liver: direct and indirect actions on nonparenchymal and parenchymal cells.","volume-title":"Int. Immunopharmacol.","year":"2001"},{"key":"2026012811255411100_R54","first-page":"2660","article-title":"Natural autoantibodies and complement promote the uptake of a self-antigen, human thyroglobulin, by B cells and the proliferation of thyroglobulin-reactive CD4+ T cells in healthy individuals.","volume-title":"Eur. J. Immunol.","year":"2001"},{"key":"2026012811255411100_R55","first-page":"531","article-title":"Function of C3 in a humoral response: iC3b\/C3dg bound to an immune complex generated with natural antibody and a primary antigen promotes antigen uptake and the expression of costimulatory molecules by all B cells, but only stimulates immunoglobulin synthesis by antigen-specific B cells.","volume-title":"Clin. Exp. Immunol.","year":"1996"},{"key":"2026012811255411100_R56","first-page":"1443","article-title":"A specific role for B cells in the generation of CD8 T cell memory by recombinant Listeria monocytogenes.","volume-title":"J. Immunol.","year":"2003"},{"key":"2026012811255411100_R57","first-page":"511","article-title":"Genetically determined resistance to listeriosis is associated with increased accumulation of inflammatory neutrophils and macrophages which have enhanced listericidal activity.","volume-title":"Immunology","year":"1985"},{"key":"2026012811255411100_R58","first-page":"163","article-title":"The role of the CD19\/CD21 complex in B cell processing and presentation of complement-tagged antigens.","volume-title":"J. Immunol.","year":"2001"},{"key":"2026012811255411100_R59","first-page":"164","article-title":"Modulation of antigen processing and presentation by covalently linked complement C3b fragment.","volume-title":"Immunology","year":"1995"},{"key":"2026012811255411100_R60","first-page":"1588","article-title":"Early local generation of C5a initiates the elicitation of contact sensitivity by leading to early T cell recruitment.","volume-title":"J. Immunol.","year":"2000"},{"key":"2026012811255411100_R61","first-page":"4018","article-title":"Human T cells express the C5a receptor and are chemoattracted to C5a.","volume-title":"J. Immunol.","year":"1999"},{"key":"2026012811255411100_R62","first-page":"1923","article-title":"A further link between innate and adaptive immunity: C3 deposition on antigen-presenting cells enhances the proliferation of antigen-specific T cells.","volume-title":"Int. Immunol.","year":"1998"},{"key":"2026012811255411100_R63","first-page":"6599","article-title":"Activated human T lymphocytes express a functional C3a receptor.","volume-title":"J. Immunol.","year":"2000"},{"key":"2026012811255411100_R64","first-page":"117","article-title":"Immunomodulatory functions of murine CR1\/2.","volume-title":"Immunopharmacology","year":"2000"},{"key":"2026012811255411100_R65","first-page":"393","article-title":"Regulation of B lymphocyte responses to foreign and self-antigens by the CD19\/CD21 complex.","volume-title":"Annu. Rev. Immunol.","year":"2000"},{"key":"2026012811255411100_R66","first-page":"2784","article-title":"CR1(CD35) and CR2(CD21) complement C3 receptors are expressed on normal human thymocytes and mediate infection of thymocytes with opsonized human immunodeficiency virus.","volume-title":"Eur. J. Immunol.","year":"1994"},{"key":"2026012811255411100_R67","first-page":"659","article-title":"Linking innate and acquired immunity: divergent role of CD46 cytoplasmic domains in T cell induced inflammation.","volume-title":"Nat. Immunol.","year":"2002"},{"key":"2026012811255411100_R68","first-page":"9","article-title":"T cell regulation: with complements from innate immunity.","volume-title":"Nat. Rev. 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