Start Date

2023

Description

Under antiretroviral therapy, the viral persistence of HIV is enabled by latent viral reservoirs, particularly in resting CD4+ T cells. Recent studies reveal interactions between endothelial cells and T cells allowing for latent infection of resting and activated CD4+ T cells. We focused our investigation on the stimulation of activated T cells by intestinal endothelial cells (IECs), due to the prominent gut pathology of HIV and predominance of an activated T cell phenotype in the gut. While prior research shows the involvement of soluble factors like IL-6 in stimulation of resting T cells, our results from transwell cultures suggest the lack of soluble factors in stimulation of activated T cells. Antibody blocking shows the involvement of integrin ICAM in IEC stimulation of activated T cells but not VCAM or MAdCAM. MAPK11 and BCL6 were upregulated in IEC stimulated activated T cells from an RNAseq. However, chemical inhibitors for these gene products did not block HIV infection in IEC stimulated T cells, indicating lack of involvement. Antibody blocking also shows lack of involvement of co-stimulatory molecule CD2. Though further research is needed, our study yielded valuable insight into the IEC and activated T cell interaction.

Share

COinS
 
Jan 1st, 12:00 AM

Mechanisms of stimulation by Intestinal Endothelial Cells during HIV infection of Activated CD4+ T cells

Under antiretroviral therapy, the viral persistence of HIV is enabled by latent viral reservoirs, particularly in resting CD4+ T cells. Recent studies reveal interactions between endothelial cells and T cells allowing for latent infection of resting and activated CD4+ T cells. We focused our investigation on the stimulation of activated T cells by intestinal endothelial cells (IECs), due to the prominent gut pathology of HIV and predominance of an activated T cell phenotype in the gut. While prior research shows the involvement of soluble factors like IL-6 in stimulation of resting T cells, our results from transwell cultures suggest the lack of soluble factors in stimulation of activated T cells. Antibody blocking shows the involvement of integrin ICAM in IEC stimulation of activated T cells but not VCAM or MAdCAM. MAPK11 and BCL6 were upregulated in IEC stimulated activated T cells from an RNAseq. However, chemical inhibitors for these gene products did not block HIV infection in IEC stimulated T cells, indicating lack of involvement. Antibody blocking also shows lack of involvement of co-stimulatory molecule CD2. Though further research is needed, our study yielded valuable insight into the IEC and activated T cell interaction.