       Document 0137
 DOCN  M95B0137
 TI    Self-reactive anti-class II T helper type 2 cell lines derived from gold
       salt-injected rats trigger B cell polycolonal activation and transfer
       autoimmunity in CD8-depleted normal syngeneic recipients.
 DT    9511
 AU    Saoudi A; Castedo M; Nochy D; Mandet C; Pasquier R; Druet P; Pelletier
       L; INSERM U 28, Hopital Broussais, Paris, France.
 SO    Eur J Immunol. 1995 Jul;25(7):1972-9. Unique Identifier : AIDSLINE
       MED/95347397
 AB    Brown Norway (BN) rats given gold salts develop an autoimmune syndrome
       with an immune complex-type glomerulonephritis in the context of a
       polyclonal B cell activation that was suspected to be due to the
       emergence of anti-self major histocompatibility complex (MHC) class II T
       cells. In the present study, six anti-self MHC class II T cell lines
       have been derived from six gold salt-treated rats by repeated
       stimulations with normal syngeneic MHC class II-bearing cells. The T
       cell lines proliferated in the presence of self MHC class II-positive B
       cell-enriched or B cell-depleted cells and the proliferation was
       inhibited by preincubating stimulator cells with an anti-IA monoclonal
       antibody. The T cell lines produced interleukin (IL)-4 only or IL-4 and
       some interferon (IFN)-gamma and could, therefore, be considered as T
       helper type 2 (Th2) and Th0 cells, respectively. They triggered normal
       syngeneic B cells to produce in vitro IgE, anti-DNA, anti-laminin and
       anti-2,4-6-trinitrophenol antibodies through, at least in part, cognate
       interactions. More interestingly, these lines when transferred into
       normal BN rats induced an autoimmune syndrome similar to or even more
       severe than the one observed in the active gold model, provided the
       recipients were CD8 depleted. These manifestations included a dramatic
       increase in serum IgE concentration and the production of anti-DNA and
       anti-laminin antibodies. In addition, all recipients displayed an
       autoimmune glomerulonephritis due to anti-laminin antibodies, granular
       IgG deposits in the interstitium, in the vessel walls and along the
       tubular basement membranes and a severe tubulointerstitial nephritis
       with marked mononuclear cell infiltration. An anti-ovalbumin T cell line
       that produced IL-4 and low amounts of IFN-gamma was used as a control
       and did not induce autoimmunity. These results demonstrate for the first
       time the ability of autoreactive Th2 as well as Th0 cell lines to induce
       antibody-mediated autoimmunity. They also show that CD8+ cells play a
       crucial role in the control of such autoreactive cells. Finally, this
       work suggests that Th2 cells could initiate cell-mediated reactions
       either directly or indirectly.
 DE    Animal  *Autoimmunity  B-Lymphocytes/*IMMUNOLOGY  Cytokines/BIOSYNTHESIS
       CD8-Positive T-Lymphocytes/*IMMUNOLOGY  Gold/*PHARMACOLOGY
       Histocompatibility Antigens Class II/*IMMUNOLOGY  IgE/BIOSYNTHESIS
       Immunity, Cellular  Immunization, Passive  Lymphocyte Depletion
       *Lymphocyte Transformation  Rats  Rats, Inbred BN  Rats, Inbred Lew
       Support, Non-U.S. Gov't  Th2 Cells/*IMMUNOLOGY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

