This Research Topic is the second volume in this series, Resident Memory T Cells: Guardians of the Balance of Local Immunity and Pathology. You can view Volume I here.

As we learn more about the intricacies of immune interactions, the goalposts of ideal vaccination strategies change. It has become apparent that for many pathogens, immunizations should seek to optimize lymphocyte-mediated protection at their portals of entry, which is not likely to be accomplished with current intramuscular jabs. However, there are increased reports suggesting resident memory CD4 and CD8 T cells may, or indeed do, cause pathologies in the lung, gut, skin, pancreas, CNS, and adipose tissue. This is following chronic infection, immunization, or sensitization and it is becoming clearer that protective immunity ought to be finely balanced with the pathogenic capacity of the resident cells providing the immunity. Alternatively, in instances like asthma or inflammatory bowel disease (IBD) where the bulk of resident CD4 or CD8T cells’ pathogenic capacity is not restrained, understanding the mechanisms of escape from immune regulation may be key. Thus we are interested in soliciting works that seek to provide a deeper mechanistic understanding of the balance of immunity and pathology that local resident memory T cells must successfully display in order to build upon the existing dogma regarding ideal vaccination strategies.

Recent works suggest that the density of resident memory T cells (TRM) is determined early in an immune response to pathogens or allergens by local players. The magnitude of TRM differentiation is key to developing sterilizing immunity against pathogen re-encounter or in the case of asthma and inflammatory bowel diseases, proportional to the degree of pathology they mediate. Key mechanisms specific to the local environment that regulate TRM density are under-explored, but vital to modulate vaccination strategies. Following infection, TRM are tightly regulated in their resident tissues and have not been widely reported to mediate pathology. However, recent work indicates that even after an infection is cleared, if a single inhibitory signal is lost or interfered with, TRM can cause severe local pathology even if strong T Cell Receptor signaling is not present. We currently know very little of these local regulatory networks that keep TRM function in check and assure they only function when foreign antigen is re-encountered. Yet to formulate safe efficacious vaccines that manipulate local T cell immunity, is a milestone worthy of exploration. We welcome Original Research, Review, Mini Reviews, Methods, Case Reports, and Clinical Trial articles related to, but not limited to, the following topics:

• Works that further the understanding of pathology or homeostatic mechanisms, such as immune status, that prevent pathology, mediated by resident-memory T cells in infections, immunizations, or sensitization.

• Works that clarify resident memory T cell niches and quorum sensing mechanisms that fill the niches and restrain detrimental clonal expansion

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Frontiers in Immunology

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