Differential Gene Expression of Soluble CD8+ T-cell mediated suppression of HIV replication in three older children - GSE23183

Goal: To compare the gene expression profiles from pediatric patients with each other, with those reported in adults and in those related to exosomes.

Background: Suppression of human immunodeficiency virus (HIV) replication by CD8+ T-cells (CD8 suppression) contributes to survival in adults and children < 1 year. Soluble CD8 suppression can also be seen in some older children with AIDS. The factor responsible, CD8-derived antiviral factor (CAF), acts at the level of HIV RNA transcription. Differential gene expression techniques have been used to define the gene(s) mediating this phenomenon in adults. Recently, CAF has been linked to exosomes secreted by CD8+ T-cells.

Objective: To compare the gene expression profiles from pediatric patients with each other, with those reported in adults and in those reportedly related to exosomes.

Design/Methods: We used differential gene expression to study 3 older children with HIV infection, 1 who did demonstrate soluble CD-8 suppression and 2 who did not, and compared our results with those reported in 2 previous studies in adults and their relatedness to exosome components secreted by CD8+ T-cells.

Results: 18 differentially expressed genes were also seen in 1 adult study (p=0.002, ?2 test), and 38 such genes (p < 0.0001, ?2 test) in a second adult study. In addition, two exosome components and some RNA’s related to exosomal proteins were also differentially expressed.

Conclusions: In children with HIV infection, we found significant differentially expressed genes that correlated to those previously reported in 2 studies in adults. Our data also lends some support to the recent identification of CAF with exosomes secreted by CD8+ T-cells.

Differential gene expression was used to study 3 older children with HIV infection, 1 who did demonstrate soluble CD-8 suppression and 2 who did not, and compared our results with those reported in 2 previous studies in adults and their relatedness to exosome components secreted by CD8+ T-cells.

Three vertically-HIV-1-infected adolescent boys were studied. This study was approved by the Children’s Memorial Institutional Review Board. After informed consent was obtained, 20 - 40 ml of heparinized peripheral blood was collected in association with regularly scheduled, clinically-indicated blood sampling.

Keywords: differential gene expression; soluble CD8 suppression; gene array; pediatric HIV infection; CD8-derived antiviral factor