6th Clinical Microbiology Conference

Biography

Biography: Annika C Karlsson

Abstract

During chronic HIV-1 infection, CD8+ T cells display a loss of effector functions. These dysfunctiona CD8+ T cells also up-regulate inhibitory molecules, such as PD-1, 2B4, CD160, a process referred to as T cell exhaustion. Recently a new inhibitory molecule, T cell immunoglobulin and ITIM domain (TIGIT), expressed on T cells was shown to inhibit their function. In addition its co-stimulatory receptor CD226 and ligan PVR is severely altered in in chronic viral infections and human cancers. However, it remains to be identified if the TIGIT/ CD226/PVR axis is dysregulated during HIV infection and linked to CD8+ T cell exhaustion. We found an increased expression of TIGIT on bulk and HIV-specific CD8+ T cells that was linked to expression of PD-1, CD160 and 2B4. On HIV-specific cells the increase in TIGIT expression was coupled to a decreased expression of CD226. Furthermore, TIGIThi cells was less common in elite controller subjects, compared to treatment naïve and long-term treated subjects and the TIGIThi cells were linked to a decreased functional capacity (IFN-γ, TNF, granzyme B & CD107a). As TIGIT needs to bind its ligand, PVR, in order to inhibit T cell function, we next measured PVR expression on CD4+ T cells in blood and lymph node. PVR expression was elevated on CD4+ T cells, especially T follicular helper (Tfh) cells which is a major reservoir for HIV-1. In summary, the TIGIT/CD226/PVR axis is altered in HIV-infected subjects, a process which was linked to a decreased functional capacity as well as an upregulation of PVR on Tfh cells. These findings highlight the importance of the TIGIT/CD226/PVR axis in the context of HIV-infection and demonstrate an immune checkpoint barrier that potentially could hinder future cure approaches mediating cellular killing of HIV-1 infected Tfh cells.