Lymph Node HIV-specific CD8 T Cells of HIV Controllers Harbour a Specific Transcriptomic Signature

Erica Lana – Allergology and Immunology – Centre Hospitalier Universitaire Vaudoise; Philippe Guillaume – Ludwig Institute for Cancer Research; Mathilde Foglierini – Allergology and Immunology – Centre Hospitalier Universitaire Vaudoise; Riddhima Banga – Allergology and Immunology – Centre Hospitalier Universitaire Vaudoise; Francesco Procopio – Allergology and Immunology – Centre Hospitalier Universitaire Vaudoise; Matthias Cavassini – Infectious diseases – Centre Hospitalier Universitaire Vaudoise; Yannick Muller – Allergology and Immunology – Centre Hospitalier Universitaire Vaudoise; Sébastien Déglise – Vascular Surgery – Centre Hospitalier Universitaire Vaudoise; Alexandre Harari – Ludwig Institute for Cancer Research; Giuseppe Pantaleo – Allergology and Immunology – Centre Hospitalier Universitaire Vaudoise; Matthieu Perreau – Allergology and Immunology – Centre Hospitalier Universitaire Vaudoise

Abstract Text: Background. CD8 T cells have a preponderant role in controlling chronic infections. However, the precise mechanisms underlying the immune-mediated control of HIV replication remains to be identified. Lymph nodes (LN) represent a major site of viral persistence, but the study of anti-HIV CD8 T cells has been largely limited to peripheral blood. An in-depth characterization of LN HIV-specific CD8 T cells of HIV controllers may identify key determinants associated to viral suppression.
Methods. We characterized blood and LN HIV-specific CD8 T cells from 5 chronic HIV infected individuals (CHI) and 4 HIV controllers by scRNA-seq and scTCR-seq. Longitudinal blood samples collected from 3 HIV controllers were also evaluated.
Results. The cumulative data indicated that LN HIV-specific CD8 T cells of HIV controllers were enriched in a specific transcriptomic profile characterized by stemness markers (i.e. TCF7, IL7R, SELL), suggesting enhanced self-renewal capacity. This stem-like population in LN also expressed EBI2, responsible for T-B cell border positioning, and the effector molecule granzyme K. Canonical cytotoxic cells were enriched in blood but rare in LN in both CHI and HIV controllers. Longitudinal TCR sequencing revealed an evolution of TCR repertoire in some controllers, with expansion of formerly subdominant clonotypes.
Conclusions. This study suggests that LN HIV-specific CD8 T cells in HIV controllers harbor a specific “stem-like” transcriptomic signature, possibly underlying an enhanced proliferative potential associated with an appropriate positioning. Interestingly, the TCR repertoire of HIV-specific CD8 T cells of HIV controllers can evolve with time, suggesting a dynamic adaptation of the immune response.