       Document 0481
 DOCN  M9610481
 TI    Role of B70/B7-2 in CD4+ T-cell immune responses induced by dendritic
       cells.
 DT    9601
 AU    Fagnoni FF; Takamizawa M; Godfrey WR; Rivas A; Azuma M; Okumura K;
       Engleman EG; Department of Pathology, Stanford University School of
       Medicine,; California, USA.
 SO    Immunology. 1995 Jul;85(3):467-74. Unique Identifier : AIDSLINE
       MED/96005840
 AB    Dendritic cells (DC) are potent antigen-presenting cells (APC). However,
       the molecular basis underlying this activity remains incompletely
       understood. To address this question, we generated murine monoclonal
       antibodies (mAb) against human peripheral blood-derived DC. One such
       antibody, designated IT209, stained differentiated DC and adherent
       monocytes, but failed to stain freshly isolated peripheral blood
       mononuclear cells (PBMC). The antigen recognized by IT209 was identified
       as B70 (B7-2; also recently identified as CD86). Using this mAb we
       studied the role of B70 in CD4+ T-cell activation by DC in vitro. IT209
       partly inhibited the proliferative response of CD4+ T cells to
       allogeneic DC and to recall antigens, such as tetanus toxoid (TT) and
       purified protein derivative (PPD) of tuberculin, presented by autologous
       DC. More importantly, the mAb had a potent inhibitory effect on the
       primary response of CD4+ T cells to autologous DC pulsed with human
       immunodeficiency virus (HIV) gp160 or keyhole limpet haemocyanin (KLH).
       Adherent monocytes, despite their expression of B70, failed to induce
       T-cell responses to these antigens. IT209-mediated inhibition of CD4+
       T-cell responses was equivalent to that produced by anti-CD25 mAb,
       whereas an anti-CD80 mAb was only marginally inhibitory and did not
       augment the effect of IT209. These findings indicate that the B70
       antigen plays an important role in DC-dependent CD4+ T-cell activation,
       particularly in the induction of primary CD4+ T-cell responses to
       soluble antigens. However, since activated monocytes, despite their
       expression of B70, failed to prime naive T cells to these antigens, our
       results suggest that additional molecules contribute to the functions of
       DC in CD4+ T-cell activation.
 DE    Antibodies, Monoclonal/IMMUNOLOGY  Antigens/IMMUNOLOGY  Antigens,
       CD/*IMMUNOLOGY  Cell Division/IMMUNOLOGY  CD4-Positive
       T-Lymphocytes/*IMMUNOLOGY  Dendritic Cells/*IMMUNOLOGY  Gene Products,
       env/IMMUNOLOGY  Human  Leukocytes, Mononuclear/IMMUNOLOGY  Lymphocyte
       Transformation/*IMMUNOLOGY  Membrane Glycoproteins/*IMMUNOLOGY
       Monocytes/IMMUNOLOGY  Protein Precursors/IMMUNOLOGY  Support, U.S.
       Gov't, Non-P.H.S.  Support, U.S. Gov't, P.H.S.  Tetanus
       Toxoid/IMMUNOLOGY  Tuberculin/IMMUNOLOGY  JOURNAL ARTICLE

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

