Combination Immune Checkpoint Blockade to Reverse HIV Latency
Renee M Van der Sluis, Nitasha A Kumar, Rachel D Pascoe, Jennifer M Zerbato, Vanessa A Evans, Ashanti I Dantanarayana, Jenny L Anderson, Rafick P Sekaly, Remi Fromentin, Nicolas Chomont, Paul U Cameron, Sharon R Lewin
Journal of Immunology | AMER ASSOC IMMUNOLOGISTS | Published : 2020
In people living with HIV on antiretroviral therapy, HIV latency is the major barrier to a cure. HIV persists preferentially in CD4+ T cells expressing multiple immune checkpoint (IC) molecules, including programmed death (PD)-1, T cell Ig and mucin domain-containing protein 3 (TIM-3), lymphocyte associated gene 3 (LAG-3), and T cell immunoreceptor with Ig and ITIM domains (TIGIT). We aimed to determine whether these and other IC molecules have a functional role in maintaining HIV latency and whether blocking IC molecules with Abs reverses HIV latency. Using an in vitro model that establishes latency in both nonproliferating and proliferating human CD4+ T cells, we show that proliferating ce..View full abstract
Awarded by Foundation for AIDS Research
Awarded by National Health and Medical Research Council (NHMRC) of Australia
Awarded by National Institutes of Health Delaney AIDS Research Enterprise to Find a Cure Collaboratory
This work was supported by funds from The Foundation for AIDS Research (Grants 108237-51-RGRL and 109226-58-RGRL), the National Health and Medical Research Council (NHMRC) of Australia (Grants APP1041795 and APP3162044), and the National Institutes of Health Delaney AIDS Research Enterprise to Find a Cure Collaboratory (Grant UM1AI126611-01). S.R.L. is an NHMRC Practitioner Fellow.