Rapid development of murine AIDS is dependent of signals provided by CD54 and CD11a.
Murine AIDS (MAIDS) is induced by infection with the replication-defective virus (BM5def) component in the LP-BM5 murine leukemia virus (MuLV) mixture. The disease is characterized by polyclonally activated CD4+ T cells and B cells. It is known that BM5def is expressed at highest levels in B lymphocytes and that B cells serve as viral antigen-presenting cells. Full and sustained activation of CD4+ T cells against a conventional Ag usually requires both TCR and costimulating signals. Among various molecules known to provide costimulatory function, the expression of CD54 (ICAM-1) and CD11a/CD18 (LFA-1) on MAIDS B cells was increased, whereas that of CD2, heat-stable Ag (CD24), CD80 (B7-1), and CD86 (B7-2) was unchanged from normal. C57BL/6 mice depleted of both CD54 and CD11a expression as a result of chronic administration of mAb had developed no MAIDS at 4 wk and 8 wk after LP-BM5 MuLV infection. In addition, the proliferative response of B cells to mitogen was well conserved, whereas MAIDS-associated increases in serum Ig levels were inhibited. Replication of BM5def was suppressed markedly in infected mice treated with the CD54 and CD11a mAbs. These results suggest that the CD54/CD11a signal transduction pathway is a critical determinant of MAIDS development, and the lack of an immune response against viral Ag is enough to suppress BM5def replication and to prevent MAIDS.
Makino
M
M
Department of Bacterial and Blood Products, National Institute of Health Japan, Tokyo.
Yoshimatsu
K
K
Azuma
M
M
Okada
Y
Y
Hitoshi
Y
Y
Yagita
H
H
Takatsu
K
K
Komuro
K
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D015703:Antigens, CD / Q000276:immunology; D002450:Cell Communication / Q000276:immunology; D005260:Female; D006942:Hypergammaglobulinemia / Q000517:prevention & control; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology*; D009052:Leukemia Virus, Murine / Q000472:pathogenicity; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016183:Murine Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology*; D014779:Virus Replication / Q000276:immunology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1