CD38 modulates CD8 TRM responses after respiratory viral infection

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Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B656
Abstract ID: 5424

Presenting Author:
Gislane de Almeida Santos , CD38 modulates CD8 TRM responses after respiratory viral infection at Univ. of Virginia Sch. of Med.

Abstract:

Aged hosts have increased susceptibility to develop persistent pathology and sustained inflammation after exposure to respiratory viral infection. Our group previously demonstrated that this condition is associated with an exuberant CD8 tissue resident memory (T_RM) cell response. However, the underlying mechanisms that contribute to exuberant T_RM accumulation and pathological activity in this context are still unknown. We found that CD8 T_RM cells isolated from the lungs of influenza-infected young and aged mice express high levels of CD38. Interestingly, aging further increases the expression of this molecule on CD8 T_RMs. CD38 is a molecule with NAD-depleting activity, which can affect a broad diversity of cellular processes. To address the physiological consequence of high expression of CD38 by CD8 T_RMs in the lung during influenza infection, young CD38^KO mice and Wild type (WT) mice were infected with influenza. We observed reduced numbers of antigen specific CD8 T_RMs in the lung of infected CD38^KO mice compared with infected WT mice. Mixed bone marrow chimera (1:1 ratio) experiments showed decreased frequency of antigen specific CD8 T cells in the lungs following CD38 deficiency, demonstrating an intrinsic role for CD38 in CD8 T_RM responses. Similar results were observed in CD8 T cell-specific CD38-deficient mice (CD38^fl/flCD8^cre). Together these results show an important role for CD38 in modulating CD8 T_RM responses in the lung during influenza infection.