The effect of allogeneic in vitro stimulation and in vivo immunization on memory CD4+ T-cell APOBEC3G expression and HIV-1 infectivity

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. © 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.