HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Hattori, S. Articles by Shirai, T. Search for Related Content PubMed PubMed Citation Articles by Hattori, S. Articles by Shirai, T.

L-Selectin-Specific Autoantibodies in Murine Lupus: Possible Involvement in Abnormal Homing and Polarization of CD4⁺ T Cell Subsets¹

Susumu Hattori^*, Hiroyuki Nishimura^*,, Hiromichi Tsurui^*, Masayuki Kato, Naoki Endo, Masaaki Abe^*, Shin Akakura^*, Kenichi Mitsui^*, Sho Ishikawa^*, Sachiko Hirose^* and Toshikazu Shirai^2,*

^* Department of Pathology, Juntendo University School of Medicine, Hongo Bunkyo-ku, Tokyo, Japan; and Toin Human Science and Technology Center, Toin University of Yokohama, Kurogane-cho, Aoba-ku, Yokohama.

One notable functional abnormality in murine and human systemic lupus erythematosus (SLE) is the defect in the production of IL-2 in association with the deficit in naive CD4⁺ T cells. The mechanism is unknown, but one idea is that naturally occurring autoantibodies with specificities to the naive CD4⁺ T cell subpopulation are related to this event. We selected hybridoma monoclonal autoantibodies from SLE-prone (New Zealand Black (NZB) x New Zealand White (NZW))F₁ mice that reacted with restricted populations of CD4⁺ T cells. One of these, H32, was specific for L-selectin, as determined by 1) distribution of Ag H32 on lymphoid cells similar to Mel-14, an epitope of L-selectin; 2) shedding of 80-kDa molecules with epitope H32 from the surface of lymph node cells coincidentally with Mel-14, when stimulated with phorbol ester; 3) cross-inhibitory activities on Ag binding between H32 and Mel-14; and 4) reactivity of H32 with recombinant mouse L-selectin. Pretreatment of ⁵¹Cr-labeled lymphocytes from BALB/c mice with H32 significantly inhibited their homing to lymph nodes in vivo. The BALB/c splenic H32⁺ CD4⁺ T cell subset produced few cytokines except IL-2, thus corresponding to naive ThP-type cells. This subset was markedly selectively depleted in aged (NZB x NZW)F₁ mice. There was an age-associated increase in frequencies and titers of anti-L-selectin autoantibodies in sera from (NZB x NZW)F₁ mice. Thus, abnormalities of naive CD4⁺ T cell subset, including IL-2 production in subjects with SLE, are at least partly attributed to the generation of autoantibodies to L-selectin.