Memory CD4+ T cells that co-express PD1 and CTLA4 have reduced response to activating stimuli facilitating HIV latency
Thomas A. Rasmussen, Jennifer M. Zerbato, Ajantha Rhodes, Carolin Tumpach, Ashanti Dantanarayana, James McMahon, Jillian S. Y. Lau, Judy Chang, Céline Gubser, Wendy J. Brown, Rebecca Hoh, Melissa Krone, Rachel D. Pascoe, Chris Chiu, Michael Bramhall, Hyun Jae Lee, Ashraful Haque, Rémi Fromentin, Nicolas Chomont, Jeffrey M. Milush, Renée M. van der Sluis, Sarah Palmer, Steven G. Deeks, Paul Cameron, Vanessa A. Evans, Sharon R. Lewin
Abstract
) cells but still have a lower proportion of cells producing multiply spliced HIV RNA after stimulation as well as reduced upregulation of T cell activation and proliferation markers. Transcriptomics analyses identify differential expression of key genes regulating T cell activation and proliferation with MAF, KLRB1, and TIGIT being upregulated in double-positive compared with double-negative cells, whereas FOS is downregulated. We conclude that, in addition to being enriched for HIV DNA, double-positive cells are characterized by negative signaling and a reduced capacity to respond to stimulation, favoring HIV latency.