4.7 Article

Viral MHCI inhibition evades tissue-resident memory T cell formation and responses

Journal

JOURNAL OF EXPERIMENTAL MEDICINE
Volume 216, Issue 1, Pages 117-132

Publisher

ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20181077

Keywords

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Funding

  1. National Institutes of Health (NIH) [U19-AI109948]
  2. Initiative for Maximizing Student Development [R25GM103757]
  3. Chancellor's Graduate Fellowship
  4. American Society for Microbiology Robert D. Watkins Graduate Research Fellowship
  5. National Cancer Institute (Cancer Center Support grant) [P30 CA91842]
  6. National Center for Research Resources, a component of the NIH (ICTS/CTSA) [ULTR002345]
  7. NIH Roadmap for Medical Research

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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 TRMs 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.

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