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Rapid development of murine AIDS is dependent of signals provided by CD54 and CD11a
M Makino1, K Yoshimatsu, M Azuma
1Department of Bacterial and Blood Products, National Institute of Health Japan, Tokyo.
Abstract:
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.
Insights
Murine AIDS (MAIDS) development is prevented by blocking CD54 and CD11a interactions. This blockade suppresses viral replication and inhibits MAIDS progression, highlighting a critical pathway for disease prevention.
Area of Science:
- Immunology
- Virology
- Molecular Biology
Background:
- Murine AIDS (MAIDS) is caused by the LP-BM5 murine leukemia virus (MuLV) mixture, specifically the replication-defective BM5def component.
- MAIDS is characterized by the polyclonal activation of CD4+ T cells and B cells, with B cells acting as viral antigen-presenting cells.
Purpose of the Study:
- To investigate the role of the CD54/CD11a signaling pathway in MAIDS pathogenesis.
- To determine if blocking this pathway can prevent MAIDS development and suppress viral replication.
Main Methods:
- Mice were treated with monoclonal antibodies (mAbs) against CD54 (ICAM-1) and CD11a (LFA-1) to deplete their expression.
- LP-BM5 MuLV infection was administered to treated and control mice.
- MAIDS development, viral replication, B cell proliferation, and serum immunoglobulin levels were assessed.
Main Results:
- Mice depleted of CD54 and CD11a expression did not develop MAIDS at 4 and 8 weeks post-infection.
- B cell proliferation was preserved, and MAIDS-associated increases in serum Ig levels were inhibited.
- BM5def replication was significantly suppressed in mice treated with CD54 and CD11a mAbs.
Conclusions:
- The CD54/CD11a signal transduction pathway is a critical determinant in the development of MAIDS.
- Inhibiting this pathway suppresses viral replication and prevents MAIDS, suggesting a novel therapeutic target.