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Evidence for a continued requirement for CD40/CD40 ligand (CD154) interactions in the progression of LP-BM5 retrovirus-induced murine AIDS.

Authors :
Green KA
Noelle RJ
Green WR
Source :
Virology [Virology] 1998 Feb 15; Vol. 241 (2), pp. 260-8.
Publication Year :
1998

Abstract

In genetically susceptible C57BL/6 mice the LP-BM5 isolate of murine retroviruses causes profound splenomegaly, lymphadenopathy, hypergammaglobulinemia, and an immunodeficiency syndrome bearing many similarities to the pathologies seen in AIDS. Because of these similarities, which also include terminal B cell lymphoma formation, this syndrome has been called murine AIDS or MAIDS. Prompted by previous reports showing that the onset of MAIDS is dependent on the presence of both CD4+ T and B cells, we have previously shown that anti-gp39/CD40 ligand mAb (anti-CD40L mAb) treatment of LP-BM5-infected mice is effective in inhibiting the induction of MAIDS when a short course of anti-CD40L mAb treatment was started on the same day as LP-BM5 administration. The success of anti-CD40L mAb therapy, as indicated by a much reduced degree of splenomegaly, hypergammaglobulinemia, and mitogen and allogeneic CTL unresponsiveness, demonstrated that CD40L/CD40 interactions were critical to the establishment of MAIDS. Here we extend these findings through the use of delayed anti-CD40L mAb treatment of mice, beginning 3-4 weeks after LP-BM5 infection, by showing that interruption of CD40L/CD40 interactions also interferes with the progression of MAIDS. About 60% of LP-BM5-preinfected mice were affected by delayed anti-CD40L mAb treatment, with substantially reduced spleen weights and serum hypergammaglobulinemia and normal or greatly restored proliferative responses to Con A stimulation and CTL responses to allogeneic stimulation. The other LP-BM5-infected mice that did not respond to anti-CD40L therapy were found to have made antibodies to the anti-CD40L mAb. Thus, in a majority of mice anti-CD40L mAb therapy was very effective in interfering with MAIDS pathogenesis well after the establishment of the virus infection and MAIDS symptomatology, indicating that CD40L/CD40 interactions are crucial to the maintenance and progression of the disease, as well as its initiation.

Details

Language :
English
ISSN :
0042-6822
Volume :
241
Issue :
2
Database :
MEDLINE
Journal :
Virology
Publication Type :
Academic Journal
Accession number :
9499800
Full Text :
https://doi.org/10.1006/viro.1997.8970