Attenuated Disease in SIV-Infected Macaques Treated with a Monoclonal Antibody against FasL
Acute SIVmac infection in macaques is accompanied by high levels of plasma viremia that decline with the appearance of viral immunity and is a model for acute HIV disease in man. Despite specific immune responses, the virus establishes a chronic, persistent infection. The destruction of CD4+ and C...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2007-01-01
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| Series: | Clinical and Developmental Immunology |
| Online Access: | http://dx.doi.org/10.1155/2007/93462 |
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| Summary: | Acute SIVmac infection in macaques is accompanied by high levels of plasma viremia that decline with the appearance of viral immunity and is a model for acute HIV disease in man. Despite specific immune responses, the virus establishes a chronic, persistent infection. The destruction of CD4+
and CD4- lymphocyte subsets in macaques
contributes to viral persistence and suggests the
importance of mechanisms for depleting both infected
and uninfected (bystander) cells. Bystander cell killing
can occur when FasL binds the Fas receptor on activated lymphocytes,
which include T and B cell subpopulations that are responding to the
infection. Destruction of specific immune cells could be an important
mechanism for blunting viral immunity and establishing persistent infection
with chronic disease. We inhibited the Fas pathway in vivo with a monoclonal
antibody against FasL (RNOK203). Here we show that treatment with anti-FasL
reduced cell death in circulating T and B cells, increased CTL and antibody
responses to viral proteins, and lowered the setpoint viremia. By blocking
FasL during only the first few weeks after infection, we attenuated SIVmac
disease and increased the life span for infected and treated macaques. |
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| ISSN: | 1740-2522 1740-2530 |