{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T00:15:14Z","timestamp":1769645714601,"version":"3.49.0"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2008,7,1]],"date-time":"2008-07-01T00:00:00Z","timestamp":1214870400000},"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":[[2008,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Airway hyperresponsiveness (AHR), a hallmark of asthma and several other diseases, can be modulated by \u03b3\u03b4 T cells. In mice sensitized and challenged with OVA, AHR depends on allergen-specific \u03b1\u03b2 T cells; but V\u03b31+ \u03b3\u03b4 T cells spontaneously enhance AHR, whereas V\u03b34+ \u03b3\u03b4 T cells, after being induced by airway challenge, suppress AHR. The activity of these \u03b3\u03b4 T cell modulators is allergen nonspecific, and how they develop is unclear. We now show that CD8 is essential for the development of both the AHR suppressor and enhancer \u03b3\u03b4 T cells, although neither type needs to express CD8 itself. Both cell types encounter CD8-expressing non-T cells in the spleen, and their functional development in an otherwise CD8-negative environment can be restored with transferred spleen cell preparations containing CD8+ dendritic cells (DCs), but not CD8+ T cells or CD8\u2212 DCs. Our findings suggest that CD8+ DCs in the lymphoid tissues enable an early step in the development of \u03b3\u03b4 T cells through direct cell contact. DC-expressed CD8 might take part in this interaction.<\/jats:p>","DOI":"10.4049\/jimmunol.181.1.309","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T19:04:22Z","timestamp":1397847862000},"page":"309-319","source":"Crossref","is-referenced-by-count":28,"title":["Evidence That CD8+ Dendritic Cells Enable the Development of \u03b3\u03b4 T Cells That Modulate Airway Hyperresponsiveness"],"prefix":"10.1093","volume":"181","author":[{"given":"Laura","family":"Cook","sequence":"first","affiliation":[{"name":"Department of Immunology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nobuaki","family":"Miyahara","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, National Jewish Medical and Research Center , Denver, CO 80206"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niyun","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Immunology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J M","family":"Wands","sequence":"additional","affiliation":[{"name":"Department of Immunology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Taube","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, National Jewish Medical and Research Center , Denver, CO 80206"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina L","family":"Roark","sequence":"additional","affiliation":[{"name":"Department of Immunology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Terry A","family":"Potter","sequence":"additional","affiliation":[{"name":"Department of Immunology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erwin W","family":"Gelfand","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, National Jewish Medical and Research Center , Denver, CO 80206"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca L","family":"O'Brien","sequence":"additional","affiliation":[{"name":"Department of Immunology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Willi K","family":"Born","sequence":"additional","affiliation":[{"name":"Department of Immunology"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2008,7,1]]},"reference":[{"key":"2026012807103047700_R1","first-page":"255","article-title":"Immunologic basis of antigen-induced airway hyperresponsiveness","volume-title":"Annu. Rev. Immunol.","year":"1999"},{"key":"2026012807103047700_R2","first-page":"2261","article-title":"Requirement for IL-13 independently of IL-4 in experimental asthma","volume-title":"Science","year":"1998"},{"key":"2026012807103047700_R3","first-page":"1869","article-title":"Regulation of IgE responses to inhaled antigen in mice by antigen-specific \u03b3\u03b4 T cells","volume-title":"Science","year":"1994"},{"key":"2026012807103047700_R4","first-page":"1265","article-title":"Requirement for \u03b3\u03b4 T cells in allergic airway inflammation","volume-title":"Science","year":"1998"},{"key":"2026012807103047700_R5","first-page":"1150","article-title":"Negative regulation of airway responsiveness that is dependent on \u03b3\u03b4 T cells and independent of \u03b1\u03b2 T cells","volume-title":"Nat. Med.","year":"1999"},{"key":"2026012807103047700_R6","first-page":"582","article-title":"Essential role of NKT cells producing IL-4 and IL-13 in the development of allergen-induced airway hyperreactivity","volume-title":"Nat. Med.","year":"2003"},{"key":"2026012807103047700_R7","first-page":"5502","article-title":"Lung CD25 CD4 regulatory T cells suppress type 2 immune responses but not bronchial hyperreactivity","volume-title":"J. Immunol.","year":"2003"},{"key":"2026012807103047700_R8","first-page":"49","article-title":"Aerosolized anti-T-cell-receptor antibodies are effective against airway inflammation and hyperreactivity","volume-title":"Int. Arch. Allergy Immunol.","year":"2004"},{"key":"2026012807103047700_R9","first-page":"1719","article-title":"Requirement for CD8+ T cells in the development of airway hyperresponsiveness in a murine model of airway sensitization","volume-title":"J. Exp. Med.","year":"1996"},{"key":"2026012807103047700_R10","first-page":"2894","article-title":"Different potentials of \u03b3\u03b4 T cell subsets in regulating airway responsiveness: V\u03b31+ cells, but not V\u03b34+ cells, promote airway hyperreactivity, TH2 cytokines, and airway inflammation","volume-title":"J. Immunol.","year":"2004"},{"key":"2026012807103047700_R11","first-page":"2961","article-title":"Airway hyperresponsiveness through synergy of \u03b3\u03b4 T cells and NKT cells","volume-title":"J. Immunol.","year":"2007"},{"key":"2026012807103047700_R12","first-page":"8850","article-title":"MHC class I-dependent V\u03b34+ pulmonary T cells regulate \u03b1\u03b2 T cell-independent airway responsiveness","volume-title":"Proc. Natl. Acad. Sci. USA","year":"2002"},{"key":"2026012807103047700_R13","first-page":"3170","article-title":"V\u03b34+ T cells regulate airway hyperreactivity to methacholine in ovalbumin-sensitized and challenged mice","volume-title":"J. Immunol.","year":"2003"},{"key":"2026012807103047700_R14","first-page":"1324","article-title":"Reversal of established allergic airway hyperreactivity by long-term allergen challenge depends on \u03b3\/\u03b4 T cells","volume-title":"Am. J. Respir. Crit. Care Med.","year":"2003"},{"key":"2026012807103047700_R15","first-page":"2671","article-title":"Mismatched antigen prepares \u03b3\u03b4 T cells for suppression of airway hyperresponsiveness","volume-title":"J. Immunol.","year":"2005"},{"key":"2026012807103047700_R16","first-page":"1086","article-title":"Distribution and leukocyte contacts of \u03b3\u03b4 T cells in the lung","volume-title":"J. Leukocyte Biol.","year":"2005"},{"key":"2026012807103047700_R17","first-page":"245","article-title":"Dendritic cells and the control of immunity","volume-title":"Nature","year":"1998"},{"key":"2026012807103047700_R18","first-page":"296","article-title":"Human \u03b3 \u03b4 T cells induce dendritic cell maturation","volume-title":"Clin. Immunol.","year":"2002"},{"key":"2026012807103047700_R19","first-page":"1575","article-title":"CD1-mediated \u03b3\/\u03b4 T cell maturation of dendritic cells","volume-title":"J. Exp. Med.","year":"2002"},{"key":"2026012807103047700_R20","first-page":"5656","article-title":"Lyme arthritis synovial \u03b3\u03b4 T cells instruct dendritic cells via Fas ligand","volume-title":"J. Immunol.","year":"2005"},{"key":"2026012807103047700_R21","first-page":"3227","article-title":"Reciprocal stimulation of \u03b3\u03b4 T cells and dendritic cells during the anti-mycobacterial immune response","volume-title":"Eur. J. Immunol.","year":"2004"},{"key":"2026012807103047700_R22","first-page":"1386","article-title":"Potentiation of antigen-stimulated V\u03b39V\u03b42 T cell cytokine production by immature dendritic cells (DC) and reciprocal effect on DC maturation","volume-title":"J. Immunol.","year":"2006"},{"key":"2026012807103047700_R23","first-page":"364","article-title":"Polyinosinic-polycytidylic acid-mediated stimulation of human \u03b3\u03b4 T cells via CD11c dendritic cell-derived type I interferons","volume-title":"Immunology","year":"2004"},{"key":"2026012807103047700_R24","first-page":"252","article-title":"Reciprocal activating interaction between dendritic cells and pamidronate-stimulated \u03b3\u03b4 T cells: role of CD86 and inflammatory cytokines","volume-title":"J. Immunol.","year":"2005"},{"key":"2026012807103047700_R25","first-page":"587","article-title":"CD8\u03b1+ and CD8\u03b1\u2212 subclasses of dendritic cells direct the development of distinct T helper cells in vivo","volume-title":"J. Exp. Med.","year":"1999"},{"key":"2026012807103047700_R26","first-page":"1925","article-title":"Epidermal viral immunity induced by CD8\u03b1+ dendritic cells but not by Langerhans cells","volume-title":"Science","year":"2003"},{"key":"2026012807103047700_R27","first-page":"165","article-title":"Systemic activation of dendritic cells by Toll-like receptor ligands or malaria infection impairs cross-presentation and antiviral immunity","volume-title":"Nat. Immunol.","year":"2006"},{"key":"2026012807103047700_R28","first-page":"1018","article-title":"Development of the dendritic cell system during mouse ontogeny","volume-title":"J. Immunol.","year":"2004"},{"key":"2026012807103047700_R29","first-page":"9","article-title":"Cross-presentation, dendritic cell subsets, and the generation of immunity to cellular antigens","volume-title":"Immunol. Rev.","year":"2004"},{"key":"2026012807103047700_R30","first-page":"2612","article-title":"Natural killer dendritic cells have both antigen presenting and lytic function and in response to CpG produce IFN-\u03b3 via autocrine IL-12","volume-title":"J. Immunol.","year":"2005"},{"key":"2026012807103047700_R31","first-page":"19","article-title":"Steady-state and inflammatory dendritic cell development","volume-title":"Nat. Rev. Immunol.","year":"2007"},{"key":"2026012807103047700_R32","first-page":"4223","article-title":"Developmentally ordered V-J recombination in mouse T cell receptor \u03b3 locus is not perturbed by targeted deletion of the V\u03b34 gene","volume-title":"J. Immunol.","year":"1997"},{"key":"2026012807103047700_R33","first-page":"714","article-title":"Self-reactive \u03b3\u03b4 T cells are eliminated in the thymus","volume-title":"Nature","year":"1990"},{"key":"2026012807103047700_R34","first-page":"8070","article-title":"T-cell \u03b3 gene is allelically but not isotypically excluded and is not required in known functional T-cell subsets","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1987"},{"key":"2026012807103047700_R35","first-page":"1921","article-title":"Ontogenic development and tissue distribution of V\u03b31-expressing \u03b3\/\u03b4 T lymphocytes in normal mice","volume-title":"J. Exp. Med.","year":"1995"},{"key":"2026012807103047700_R36","first-page":"865","article-title":"Effector CD8+ T cells mediate inflammation and airway hyper-responsiveness","volume-title":"Nat. Med.","year":"2004"},{"key":"2026012807103047700_R37","first-page":"14741","article-title":"\u03b3 \u03b4 T cell homeostasis is established in competition with \u03b1 \u03b2 T cells and NK cells","volume-title":"Proc. Natl. Acad. Sci. USA","year":"2005"},{"key":"2026012807103047700_R38","first-page":"12063","article-title":"CD8 T cell competition for dendritic cells in vivo is an early event in activation","volume-title":"Proc. Natl. Acad. Sci. USA","year":"2006"},{"key":"2026012807103047700_R39","first-page":"41","article-title":"Antigen specific suppression of T-cell responses: the veto concept","volume-title":"Immunol. Today","year":"1985"},{"key":"2026012807103047700_R40","first-page":"1061","article-title":"Are CD8+ dendritic cells (DC) veto cells? The role of CD8 on DC in DC development and in the regulation of CD4 and CD8 T cell responses","volume-title":"Int. Immunol.","year":"1997"},{"key":"2026012807103047700_R41","first-page":"3501","article-title":"Molecular basis for the high affinity interaction between the thymic leukemia antigen and the CD8\u03b1\u03b1 molecule","volume-title":"J. Immunol.","year":"2005"},{"key":"2026012807103047700_R42","first-page":"27237","article-title":"Expression, purification and functional analysis of murine ectodomain fragments of CD8\u03b1\u03b1 and CD8\u03b1\u03b2 dimers","volume-title":"J. Biol. Chem.","year":"1999"},{"key":"2026012807103047700_R43","first-page":"8670","article-title":"Distinct migrating and nonmigrating dendritic cell populations are involved in MHC class I-restricted antigen presentation after lung infection with virus","volume-title":"Proc. Natl. Acad. Sci. USA","year":"2004"},{"key":"2026012807103047700_R44","first-page":"153","article-title":"Migratory dendritic cells transfer antigen to a lymph node-resident dendritic cell population for efficient CTL priming","volume-title":"Immunity","year":"2006"},{"key":"2026012807103047700_R45","first-page":"1685","article-title":"CD8+ but not CD8\u2212 dendritic cells cross-prime cytotoxic T cells in vivo","volume-title":"J. Exp. Med.","year":"2000"},{"key":"2026012807103047700_R46","first-page":"196","article-title":"CD8\u03b1+ dendritic cells selectively present MHC class I-restricted noncytolytic viral and intracellular bacterial antigens in vivo","volume-title":"J. Immunol.","year":"2005"},{"key":"2026012807103047700_R47","first-page":"1996","article-title":"Cutting edge: conventional CD8\u03b1+ dendritic cells are generally involved in priming CTL immunity to viruses","volume-title":"J. Immunol.","year":"2004"},{"key":"2026012807103047700_R48","first-page":"503","article-title":"Dendritic cells prime natural killer cells by trans-presenting interleukin 15","volume-title":"Immunity","year":"2007"},{"key":"2026012807103047700_R49","first-page":"2229","article-title":"Tumor necrosis factor-\u03b1 negatively regulates airway hyperresponsiveness through \u03b3\u03b4 T cells","volume-title":"Am. J. Respir. Crit. Care Med.","year":"2001"},{"key":"2026012807103047700_R50","first-page":"4190","article-title":"Requirement for the p75 TNF-\u03b1 receptor 2 in the regulation of airway hyperresponsiveness by \u03b3\u03b4 T cells","volume-title":"J. Immunol.","year":"2002"},{"key":"2026012807103047700_R51","first-page":"1936","article-title":"T cell responses modulated through interaction between CD8\u03b1\u03b1 and the nonclassical MHC class I molecule, TL","volume-title":"Science","year":"2001"},{"key":"2026012807103047700_R52","first-page":"15057","article-title":"Activation of naturally occurring lung CD4+CD25+ regulatory T cells requires CD8 and MHC I interaction","volume-title":"Proc. Natl. Acad. Sci. USA","year":"2007"},{"key":"2026012807103047700_R53","first-page":"77","article-title":"\u03b3\u03b4 T cell receptors: functional correlations","volume-title":"Immunol. Rev.","year":"2007"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/181\/1\/309\/62582945\/7311.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/181\/1\/309\/62582945\/7311.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T12:12:07Z","timestamp":1769602327000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/181\/1\/309\/8008176"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,7,1]]},"references-count":53,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2008,7,1]]},"published-print":{"date-parts":[[2008,7,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.181.1.309","relation":{},"ISSN":["1550-6606","0022-1767"],"issn-type":[{"value":"1550-6606","type":"electronic"},{"value":"0022-1767","type":"print"}],"subject":[],"published-other":{"date-parts":[[2008,7]]},"published":{"date-parts":[[2008,7,1]]}}}