The effect of allogeneic in vitro stimulation and in vivo immunization on memory CD4+ T-cell APOBEC3G expression and HIV-1 infectivity
✍ Scribed by Pido-Lopez Jeffrey; Yufei Wang; Thomas Seidl; Kaboutar Babaahmady; Robert Vaughan; Thomas Lehner
- Publisher
- John Wiley and Sons
- Year
- 2009
- Tongue
- English
- Weight
- 372 KB
- Volume
- 39
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
Abstract
Allogeneic immunity is one of the most potent natural immune responses. APOBEC3G (A3G) is an intracellular anti‐viral factor that deaminates cytidine to uridine. Allogeneic stimulation of human CD4^+^ T cells in vitro upregulated A3G mRNA and a significant correlation was found between the mixed leukocyte reaction and A3G mRNA. The mechanism of upregulation of A3G mRNA involves interaction between HLA on DC and TCR of CD4^+^ T cells, which is ZAP70 and downstream ERK phosphokinase signalling dependent and induces CD40L and A3G mRNA expression in CD4^+^ T cells. Alloimmune‐induced A3G was found to be significantly increased in CD45RA^−^, CCR5^+^ and CD45RA^−^CCR7^−^ subsets of effector memory T cells. In vivo studies of women alloimmunized with their partners' PBMC also showed a significant increase in A3G protein in CD4^+^ T cells, CD45RO^+^ memory and CCR7^−^ effector memory T cells. The functional effect of allostimulation upregulating A3G mRNA was demonstrated by a significant decrease in in vitro infectivity, using GFP‐labelled pseudovirus and confirmed by a decrease in HIV‐1 (BaL) infection of primary CD4^+^ T cells. The results suggest that alloimmunization offers an alternative or complementary strategy in inducing an innate anti‐viral factor that inhibits HIV‐1 infection.
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