TY - JOUR
T1 - Viral MHCI inhibition evades tissue-resident memory T cell formation and responses
AU - Lauron, Elvin J.
AU - Yang, Liping
AU - Harvey, Ian B.
AU - Sojka, Dorothy K.
AU - Williams, Graham D.
AU - Paley, Michael A.
AU - Bern, Michael D.
AU - Park, Eugene
AU - Victorino, Francisco
AU - Boon, Adrianus C.M.
AU - Yokoyama, Wayne M.
N1 - Funding Information:
This work was supported by the National Institutes of Health (NIH; grant U19-AI109948 and the Initiative for Maximizing Student Development grant R25GM103757), the Chancellor’s Graduate Fellowship, and the American Society for Microbiology Robert D. Watkins Graduate Research Fellowship. The GTAC is partially supported by the National Cancer Institute (Cancer Center Support grant P30 CA91842 to the Siteman Cancer Center) and by the National Center for Research Resources, a component of the NIH (ICTS/CTSA grant ULTR002345), and NIH Roadmap for Medical Research. This publication is solely the responsibility of the authors and does not necessarily represent the official view of the National Center for Research Resources or NIH. The authors declare no competing financial interests.
Funding Information:
We thank Sathi Wijeyesinghe and Dr. David Masopust for their technical advice regarding IV staining. We also gratefully acknowledge Dr. Herbert Virgin, Dr. Brian Edelson, Dr. David Sibley, and Dr. Haina Shin for their helpful suggestions on this study. We thank the GTAC, Department of Genetics, Washington University School of Medicine for help with RNA-seq analysis. This work was supported by the National Institutes of Health (NIH; grant U19-AI109948 and the Initiative for Maximizing Student Development grant R25GM103757), the Chancellor’s Graduate Fellowship, and the American Society for Microbiology Robert D. Watkins Graduate Research Fellowship. The GTAC is partially supported by the National Cancer Institute (Cancer Center Support grant P30 CA91842 to the Siteman Cancer Center) and by the National Center for Research Resources, a component of the NIH (ICTS/CTSA grant ULTR002345), and NIH Roadmap for Medical Research. This publication is solely the responsibility of the authors and does not necessarily represent the official view of the National Center for Research Resources or NIH.
Publisher Copyright:
© 2018 Lauron et al.
PY - 2019/1/1
Y1 - 2019/1/1
N2 - Tissue-resident memory CD8 + T cells (T RM s) confer rapid protection and immunity against viral infections. Many viruses have evolved mechanisms to inhibit MHCI presentation in order to evade CD8 + T cells, suggesting that these mechanisms may also apply to T RM -mediated protection. However, the effects of viral MHCI inhibition on the function and generation of T RM s is unclear. Herein, we demonstrate that viral MHCI inhibition reduces the abundance of CD4 + and CD8 + T RM s, but its effects on the local microenvironment compensate to promote antigen-specific CD8 + T RM formation. Unexpectedly, local cognate antigen enhances CD8 + T RM development even in the context of viral MHCI inhibition and CD8 + T cell evasion, strongly suggesting a role for in situ cross-presentation in local antigen-driven T RM differentiation. However, local cognate antigen is not required for CD8 + T RM maintenance. We also show that viral MHCI inhibition efficiently evades CD8 + T RM effector functions. These findings indicate that viral evasion of MHCI antigen presentation has consequences on the development and response of antiviral T RM s.
AB - Tissue-resident memory CD8 + T cells (T RM s) confer rapid protection and immunity against viral infections. Many viruses have evolved mechanisms to inhibit MHCI presentation in order to evade CD8 + T cells, suggesting that these mechanisms may also apply to T RM -mediated protection. However, the effects of viral MHCI inhibition on the function and generation of T RM s is unclear. Herein, we demonstrate that viral MHCI inhibition reduces the abundance of CD4 + and CD8 + T RM s, but its effects on the local microenvironment compensate to promote antigen-specific CD8 + T RM formation. Unexpectedly, local cognate antigen enhances CD8 + T RM development even in the context of viral MHCI inhibition and CD8 + T cell evasion, strongly suggesting a role for in situ cross-presentation in local antigen-driven T RM differentiation. However, local cognate antigen is not required for CD8 + T RM maintenance. We also show that viral MHCI inhibition efficiently evades CD8 + T RM effector functions. These findings indicate that viral evasion of MHCI antigen presentation has consequences on the development and response of antiviral T RM s.
UR - http://www.scopus.com/inward/record.url?scp=85059927918&partnerID=8YFLogxK
U2 - 10.1084/jem.20181077
DO - 10.1084/jem.20181077
M3 - Comment/debate
C2 - 30559127
AN - SCOPUS:85059927918
SN - 0022-1007
VL - 216
SP - 117
EP - 132
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 1
ER -