Tissue-specific programming of memory CD8 T cell subsets impacts protection against lethal respiratory virus infection

Abstract

Abboud et al. reveal the striking and unexpected spatial organization of central- versus effector-like memory cells within the infected lung tissue and how cooperation between these two subsets contributes to host defense.

Tissue-Specific Control of Tissue-Resident Memory T Cells

“…81 An independent investigation also confirms that CXCR3 hi and CXCR3 lo lung CD8 + T cells represent different differentiation stages in response to local inflammation (e.g., IL-12 and IL-15) and occupy distinct niches in the lung. Further, cooperative action from both CXCR3 hi and CXCR3 lo lung T RM s is required for the protection against lethal respiratory VACV challenge 12. Considering that CXCR3 hi airway-resident CD8 + T cells are established protectors against respiratory infections, 82,83 lung T RM cells may not represent a homogenous population of cells.…”

“…10,11 Comparing with T EM , T CM cells generally express higher level of chemokine receptor CXCR3, which also enhances the migration of T CM into inflamed peripheral tissues. 12 Thus, the migration pattern of memory T cells is dynamically controlled by inflammatory signals independent of antigenic stimulation.…”

HVEM Imprints Memory Potential on Effector CD8 T Cells Required for Protective Mucosal Immunity

“…To further understand the role of HVEM, we used a model of respiratory infection that involves the differentiation of SLECs and MPECs, where MPECs are essential for long-term protection against virus re-infection in the lungs (13). To efficiently track CD8 T cells, and allow specific deletion of HVEM on these cells, we used a system with adoptive transfer of OT-I CD8 T cells responding to recombinant VacV-WR expressing the full-length ovalbumin protein (rVACV-WR-OVA) given intranasally.…”

“…To further investigate the idea that HVEM controls the proportion of MPECs vs SLECs that are either generated or maintained over time, we assessed the down-regulation of CXCR3 on KLRG1 hi and KLRG1 lo CD8 T cells that we have recently demonstrated to distinguish memory subsets that localize in particular niches in the lungs in response to respiratory VacV infection (13). Interestingly, whereas the proportion of KLRG1 lo CXCR3 hi MPECs generated in the lungs when HVEM could not be expressed on CD8 T cells was reduced by approximately 2-fold (Supplementary Fig.…”

“…These cells have increased capacity to survive long-term and go on to form the bulk of the memory pool. Moreover, SLECs and MPECs can occupy different anatomical niches within the lymphoid and peripheral tissues, which might further impact their survival and homeostasis and their contribution to protection (11–13). …”