Editors' ChoiceFOCIS HIGHLIGHTS

Y’all comeback now

See allHide authors and affiliations

Science Immunology  03 May 2019:
Vol. 4, Issue 35, eaax8197
DOI: 10.1126/sciimmunol.aax8197

Abstract

Keratinocytes regulate circulating CD8+ T cell memory after cutaneous infection.

Immunologic memory ensures that successive encounters with the same pathogen lead to a swift resolution of infection. In skin, vaccinia virus (VV) infection results in the differentiation and persistence of VV-specific tissue-resident memory T cells (TRM)—a process dependent on keratinocyte αvβ6 and αvβ8 integrin-mediated activation of transforming growth factor-β (TGFβ). However, it is unknown whether a similar process influences the persistence of circulating memory CD8+ T cells. Hirai et al. address this question by characterizing populations of circulating memory CD8+ T cells after the resolution of VV infection in double-transgenic mice exhibiting a complete deletion of αvβ6 and keratinocyte-specific deletion of αvβ8.

By tracking the kinetics of VV-specific memory T cell populations, the authors show that while the fractions of memory precursors and circulating peripheral memory T cells (TPM) were unchanged during the primary response, diminishment of these populations in the spleen and skin was evident in the resolution phase and long thereafter in mice with specific deletions of αvβ6 and αvβ8 (Itgb6−/−Itgb8fl/fl-K14-cre). Additionally, the fractions of central memory T cells (TCM) and TPM splenocytes expressing the skin-homing molecules P-selectin ligand and E-selectin ligand were diminished in these mice. These results were corroborated in experiments whereby CD8+ VV-specific splenocytes from previously infected wild-type mice were adoptively transferred into double knockout and control recipients. Alternatively, the defective circulating memory phenotype was rescued when CD8+ VV-specific splenocytes expressing a constitutively active form of the TGFβ receptor were transferred into double knockout recipients. Using this same model, transfer of pertussis toxin–treated, CD8+ VV-specific splenocytes into these recipients did not alter the percentages of splenic memory populations. This suggests that local signals delivered during passage through the skin alters the requirements of circulating CD8+ memory T cells for survival and/or maintenance thereafter. Importantly, the authors show that the lack of circulating memory T cell persistence in the skin and secondary lymphoid organs in double-knockout mice resulted in reduced clearance of VV upon secondary infection. Overall, this study elegantly demonstrates that cutaneous keratinocyte activation of TGFβ following infection is required for optimal persistence of recirculating T cell memory.

Highlighted Article

View Abstract

Navigate This Article