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M9610481.TXT
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1996-01-30
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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).