{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:12:00Z","timestamp":1790035920533,"version":"4.0.1"},"reference-count":41,"publisher":"Rockefeller University Press","issue":"6","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1996,12,1]]},"abstract":"<jats:p>L-selectin, an adhesion molecule constitutively expressed on leukocytes, is important for primary adhesion and extravasation of lymphocytes at specialized high endothelial venules within lymph nodes and other leukocytes at sites of inflammation. We have generated L-selectin\u2013deficient mice by targeted disruption, and have confirmed a previously reported phenotype which includes strikingly impaired contact hypersensitivity (CHS) responses to reactive haptens (Tedder, T.F., D.A. Steeber, and P. Pizcueta. 1995. J. Exp. Med. 181:2259\u20132264; Xu, J.C., I.S. Grewal, G.P. Geba, and R.A. Flavell. 1996. 183:589\u2013598.). Since the mechanism of this impairment has not been clarified, we sought to define the stage(s) at which the CHS response is affected in L-selectin\u2013deficient mice. We show that epidermal Langerhans cells in L-selectin\u2013 deficient mice are normal in number, migrate to peripheral lymph nodes appropriately, and are functional in presenting allogeneic and haptenic antigens. Moreover, T cells, as well as neutrophil and monocyte effector populations, are fully capable of entry into the inflamed skin sites in the absence of L-selectin. Thus, antigen presentation and effector mechanisms are intact in L-selectin deficient mice. In contrast, virtually no antigen-specific T cells can be found within draining peripheral nodes after a contact challenge, suggesting that the defect resides primarily in the inability of antigen-specific T cells to home to and be activated in these nodes. Indeed, L-selectin\u2013deficient mice mount completely normal CHS responses when alternate routes of immunization are used. These studies pinpoint the lesion in CHS to a discrete stage of the afferent limb of the response, clarify the role of L-selectin on effector populations, and illustrate the critical importance of the route of antigen entry to the successful execution of an immune response.<\/jats:p>","DOI":"10.1084\/jem.184.6.2341","type":"journal-article","created":{"date-parts":[[2004,6,24]],"date-time":"2004-06-24T07:56:10Z","timestamp":1088063770000},"page":"2341-2352","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":75,"title":["The Route of Antigen Entry Determines the Requirement for L-selectin during Immune Responses"],"prefix":"10.1084","volume":"184","author":[{"given":"Michelle D.","family":"Catalina","sequence":"first","affiliation":[{"name":"From the *Laboratory of Molecular Pathology, Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas 75235-9072; \u2021Department of Dermatology, University of Texas Southwestern Medical Center, Dallas, Texas 75235-9069; and \u00a7Harvard Medical School, Department of Pathology, Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael C.","family":"Carroll","sequence":"additional","affiliation":[{"name":"From the *Laboratory of Molecular Pathology, Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas 75235-9072; \u2021Department of Dermatology, University of Texas Southwestern Medical Center, Dallas, Texas 75235-9069; and \u00a7Harvard Medical School, Department of Pathology, Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Arizpe","sequence":"additional","affiliation":[{"name":"From the *Laboratory of Molecular Pathology, Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas 75235-9072; \u2021Department of Dermatology, University of Texas Southwestern Medical Center, Dallas, Texas 75235-9069; and \u00a7Harvard Medical School, Department of Pathology, Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Takashima","sequence":"additional","affiliation":[{"name":"From the *Laboratory of Molecular Pathology, Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas 75235-9072; \u2021Department of Dermatology, University of Texas Southwestern Medical Center, Dallas, Texas 75235-9069; and \u00a7Harvard Medical School, Department of Pathology, Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pila","family":"Estess","sequence":"additional","affiliation":[{"name":"From the *Laboratory of Molecular Pathology, Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas 75235-9072; \u2021Department of Dermatology, University of Texas Southwestern Medical Center, Dallas, Texas 75235-9069; and \u00a7Harvard Medical School, Department of Pathology, Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark H.","family":"Siegelman","sequence":"additional","affiliation":[{"name":"From the *Laboratory of Molecular Pathology, Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas 75235-9072; \u2021Department of Dermatology, University of Texas Southwestern Medical Center, Dallas, Texas 75235-9069; and \u00a7Harvard Medical School, Department of Pathology, Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[1996,12,1]]},"reference":[{"key":"2023072819490550400_B1","first-page":"257","article-title":"The route of recirculation of lymphocytes in the rat","volume":"159","author":"Gowans","year":"1964","journal-title":"Philos Trans R Soc Lond Ser B Biol Sci"},{"key":"2023072819490550400_B2","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/304030a0","article-title":"A cell-surface molecule involved in organ-specific homing of lymphocytes","volume":"304","author":"Gallatin","year":"1983","journal-title":"Nature (Lond)"},{"key":"2023072819490550400_B3","doi-asserted-by":"crossref","first-page":"2068","DOI":"10.1182\/blood.V84.7.2068.2068","article-title":"Leukocyte-endothelial adhesion molecules","volume":"84","author":"Carlos","year":"1994","journal-title":"Blood"},{"key":"2023072819490550400_B4","doi-asserted-by":"crossref","first-page":"7538","DOI":"10.1073\/pnas.88.17.7538","article-title":"Two-step model of leukocyte-endothelial cell interaction in inflammation: distinct roles for LECAM-1 and the leukocyte beta 2 integrins in vivo","volume":"88","author":"Von Andrian","year":"1991","journal-title":"Proc Natl Acad Sci USA"},{"key":"2023072819490550400_B5","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1016\/0092-8674(91)90393-D","article-title":"Leukocytes roll on a selectin at physiologic flow rates: distinction from and prerequisite for adhesion through integrins","volume":"65","author":"Lawrence","year":"1991","journal-title":"Cell"},{"key":"2023072819490550400_B6","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1126\/science.3003913","article-title":"Cell surface molecule associated with lymphocyte homing is a ubiquitinated branched-chain glycoprotein","volume":"231","author":"Siegelman","year":"1986","journal-title":"Science (Wash DC)"},{"key":"2023072819490550400_B7","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1126\/science.2646713","article-title":"Mouse lymph node homing receptor cDNA clone encodes a glycoprotein revealing tandem interaction domains","volume":"243","author":"Siegelman","year":"1989","journal-title":"Science (Wash DC)"},{"key":"2023072819490550400_B8","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1084\/jem.144.3.828","article-title":"Lymphocyte homing into lymph nodes: in vitro demonstration of the selective affinity of recirculating lymphocytes for high-endothelial venules","volume":"144","author":"Stamper","year":"1976","journal-title":"J Exp Med"},{"key":"2023072819490550400_B9","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1084\/jem.183.2.589","article-title":"Impaired primary T cell responses in l-selectin\u2013deficient mice","volume":"183","author":"Xu","year":"1996","journal-title":"J Exp Med"},{"key":"2023072819490550400_B10","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/1074-7613(94)90076-0","article-title":"Lymphocyte homing and leukocyte rolling and migration are impaired in L-selectin\u2013deficient mice","volume":"1","author":"Arbones","year":"1994","journal-title":"Immunity"},{"key":"2023072819490550400_B11","doi-asserted-by":"crossref","first-page":"445","DOI":"10.4049\/jimmunol.124.1.445","article-title":"Epidermal Langerhans cell density determines whether contact hypersensitivity or unresponsiveness follows skin painting with DNFB","volume":"124","author":"Toews","year":"1980","journal-title":"J Immunol"},{"key":"2023072819490550400_B12","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1111\/1523-1747.ep12543557","article-title":"Tolerance or hypersensitivity to 2,4-dinitro1-fluorobenzene: the role of Langerhans cell density within epidermis","volume":"74","author":"Streilein","year":"1980","journal-title":"J Invest Dermatol"},{"key":"2023072819490550400_B13","doi-asserted-by":"crossref","first-page":"4535","DOI":"10.1073\/pnas.78.7.4535","article-title":"Lymphocyte function-associated antigen-1 (LFA-1): a surface antigen distinct from Lyt-2,3 that participates in T lymphocyte-mediated killing","volume":"78","author":"Davignon","year":"1981","journal-title":"Proc Natl Acad Sci USA"},{"key":"2023072819490550400_B14","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1002\/eji.1830111013","article-title":"F4\/80, a mouse monoclonal antibody directed specifically against the mouse macrophage","volume":"11","author":"Austyn","year":"1981","journal-title":"Eur J Immunol"},{"key":"2023072819490550400_B15","doi-asserted-by":"crossref","first-page":"115","DOI":"10.4049\/jimmunol.112.1.115","article-title":"Tolerance and contact sensitivity to DNFB in mice. 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