{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T10:49:20Z","timestamp":1770720560471,"version":"3.49.0"},"reference-count":56,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2005,11,17]],"date-time":"2005-11-17T00:00:00Z","timestamp":1132185600000},"content-version":"vor","delay-in-days":5618,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[1990,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In the (SWR \u00d7 NZB)F<jats:sub>1<\/jats:sub> (SNF<jats:sub>1<\/jats:sub>) model of lupus nephritis, pathogenic variety of IgG anti\u2010DNA autoantibodies are induced by certain T helper (T<jats:sub>h<\/jats:sub>) cells that are either CD4<jats:sup>+<\/jats:sup> or CD4<jats:sup>\u2212<\/jats:sup>CD8<jats:sup>\u2212<\/jats:sup> (double negative; DN) in phenotype. From the spleens of eight SNF<jats:sub>1<\/jats:sub> mice with lupus nephritis, 149 T cell lines were derived and out of these only 25 lines (\u2248 17%) were capable of augmenting the production of pathogenic anti\u2010DNA autoantibodies. Herein, we analyzed the T cell receptor (TcR) V<jats:sub>\u03b2<\/jats:sub> genes used by 16 such pathogenic autoantibody\u2010inducing T<jats:sub>h<\/jats:sub> cell lines. Twelve of the T<jats:sub>h<\/jats:sub> lines were CD4<jats:sup>+<\/jats:sup> and among these five lines expressed V<jats:sub>\u03b2<\/jats:sub>8 (8.2 or 8.3). The V<jats:sub>\u03b2<\/jats:sub>8 gene family is contributed by the NZB parent to the SNF<jats:sub>1<\/jats:sub> mice, since it is absent in the SWR parental strain. Three other CD4<jats:sup>+<\/jats:sup> T<jats:sub>h<\/jats:sub> lines expressed V<jats:sub>\u03b2<\/jats:sub>4, another was V<jats:sub>\u03b2<\/jats:sub>2<jats:sup>+<\/jats:sup> and one line with poor autoantibody\u2010inducing capability expressed V<jats:sub>\u03b2<\/jats:sub>1. Four autoantibody\u2010inducing T<jats:sub>h<\/jats:sub> lines from the SNF<jats:sub>1<\/jats:sub> mice had a DN phenotype and these lines were also autoreactive, proliferating in response to syngeneic spleen cells. Among these DN T<jats:sub>h<\/jats:sub> lines, two expressed V<jats:sub>\u03b2<\/jats:sub>6 and one expressed V<jats:sub>\u03b2<\/jats:sub>8.1 TcR. Both of these are forbidden TcR directed against Mls\u20101<jats:sup>a<\/jats:sup> (Mls<jats:sup>a<\/jats:sup>) autoantigens expressed by the SNF<jats:sub>1<\/jats:sub> mice and such autoreactive T cells should have been deleted during thymic ontogeny. Thus, the DN T<jats:sub>h<\/jats:sub> cells of non\u2010<jats:italic>lpr<\/jats:italic> SNF<jats:sub>1<\/jats:sub> mice are different from the DN cells or MRL\u2010<jats:italic>lpr<\/jats:italic> which lack helper activity and do not express forbidden TcR. The spleens of 6 out of 19 nephritic SNF<jats:sub>1<\/jats:sub> animals tested also showed an expansion of forbidden autoreactive TcR<jats:sup>+<\/jats:sup> cells that were mainly DN. Two of these animals expressed high levels of V<jats:sub>\u03b2<\/jats:sub>6 (anti\u2010Mls<jats:sup>a<\/jats:sup>) and V<jats:sub>\u03b2<\/jats:sub>11 (anti\u2010I\u2010E) TcR<jats:sup>+<\/jats:sup> cells, three others had high levels of V<jats:sub>\u03b2<\/jats:sub>11<jats:sup>+<\/jats:sup> cells alone and one animal had an expanded population of V<jats:sub>\u03b2<\/jats:sub>17a<jats:sup>+<\/jats:sup> (anti\u2010I\u2010E) cells. The I\u2010E\u2010reactive TcR again should have been eliminated in the SNF<jats:sub>1<\/jats:sub> thymus, since they express I\u2010E molecules contributed by the NZB parent. The SWR parents of SNF<jats:sub>1<\/jats:sub>, are I\u2010E<jats:sup>\u2212<\/jats:sup>; moreover, they lack the V<jats:sub>\u03b2<\/jats:sub>11 gene but they express V<jats:sub>\u03b2<\/jats:sub>17a in peripheral T cells. Whereas the NZB parents are I\u2010E<jats:sup>+<\/jats:sup>, they lack a functional V<jats:sub>\u03b2<\/jats:sub>17a gene and they delete mature V<jats:sub>\u03b2<\/jats:sub>11<jats:sup>+<\/jats:sup> T cells. Thus, a combination of MHC class II and TcR genes inherited from the NZB and SWR parents and abnormalities in thymic deletion\/selection processes may generate the autoantibody\u2010inducing T<jats:sub>h<\/jats:sub> cells in the SNF<jats:sub>1<\/jats:sub> mice.<\/jats:p>","DOI":"10.1002\/eji.1830200705","type":"journal-article","created":{"date-parts":[[2007,3,1]],"date-time":"2007-03-01T12:08:21Z","timestamp":1172750901000},"page":"1435-1443","source":"Crossref","is-referenced-by-count":29,"title":["T cell receptor V<sub>\u03b2<\/sub> genes expressed by IgG anti\u2010DNA autoantibody\u2010inducing T cells in lupus nephritis: Forbidden receptors and double\u2010negative T cells"],"prefix":"10.1002","volume":"20","author":[{"given":"Sharlene","family":"Adams","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tracy","family":"Zordan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krishna","family":"Sainis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Syamal K.","family":"Datta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,11,17]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"crossref","first-page":"2232","DOI":"10.4049\/jimmunol.131.5.2232","volume":"131","author":"Eastcott J. 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