Tissue-Resident Memory CD8+ T Cells Can Be Deleted by Soluble, but Not Cross-Presented Antigen

Abstract

Under noninflammatory conditions, both naive and central memory CD8 T cells can be eliminated in the periphery with either soluble peptide or cross-presented Ag. Here, we assess the tolerance susceptibility of tissue-resident memory CD8 T cells in mice to these two forms of tolerogen. Soluble peptide specifically eliminated the majority of memory CD8 cells present in both lymphoid and extralymphoid tissues including lung and liver, but was unable to reduce the number present in the CNS. In contrast, systemic cross-presentation of Ag by dendritic cells resulted in successful elimination of memory cells only from the spleen, with no significant reduction in the numbers of tissue-resident memory cells in the lung. The fact that tissue-resident memory cells were unable to access cross-presented Ag suggests that either the memory cells in the lung do not freely circulate out of the tissue, or that they circulate through a region in the spleen devoid of cross-presented Ag. Thus, although tissue-resident memory cells are highly susceptible to tolerance induction, both the form of tolerogen and location of the T cells can determine their accessibility to tolerogen and the degree to which they are successfully deleted from specific tissues.

Targeting T-cell memory: where do we stand?

“…injection of soluble antigen causes a short expansion phase followed by deletion of specific memory CD8 T cells. The recent follow-up study showed that this approach targets not only memory T cells in secondary lymphoid organs ('central memory'), but also those residing in the peripheral tissues ('effector memory') [31]. Analogous findings were recently published in a model using memory T cells specific for an autoantigen alphaB-crystallin [32].…”

Memory T cells as an occupying force

“…They reported that while memory cells in most tissues and organs equilibrated with kinetics similar to the mixing of the bloodstreams, memory CD8 + T cells in the brain and intestinal mucosa of partner mice did not equilibrate. Further evidence that memory CD8 + T cells in the CNS are separated from the recirculating memory pools was presented by Wei et al 18, who showed that peptide injection could not delete memory T cells in the brain although memory cells in all other tissues were deleted.…”

The emerging role of resident memory T cells in protective immunity and inflammatory disease

“…The previous explanation of the expression of CD69 was that they were in an activated state, perhaps as a result of retained antigen; however, we now know that CD69 expression is a generic characteristic of resting T RM . 29 There is good evidence that CD8 + resident memory T cells can be protective against subsequent infection with influenza. Intranasal, but not intraperitoneal infection with influenza in mice results in the presence of lung T RM , though both routes of infection efficiently produced influenza-specific T EM 30 .…”