Immune signatures of protective spleen memory CD8 T cells

Abstract

Memory CD8 T lymphocyte populations are remarkably heterogeneous and differ in their ability to protect the host. In order to identify the whole range of qualities uniquely associated with protective memory cells we compared the gene expression signatures of two qualities of memory CD8 T cells sharing the same antigenic-specificity: protective (Influenza-induced, Flu-TM) and non-protective (peptide-induced, TIM) spleen memory CD8 T cells. Although Flu-TM and TIM express classical phenotypic memory markers and are polyfunctional, only Flu-TM protects against a lethal viral challenge. Protective memory CD8 T cells express a unique set of genes involved in migration and survival that correlate with their unique capacity to rapidly migrate within the infected lung parenchyma in response to influenza infection. We also enlighten a new set of poised genes expressed by protective cells that is strongly enriched in cytokines and chemokines such as Ccl1, Ccl9 and Gm-csf. CCL1 and GM-CSF genes are also poised in human memory CD8 T cells. These immune signatures are also induced by two other pathogens (vaccinia virus and Listeria monocytogenes). The immune signatures associated with immune protection were identified on circulating cells, i.e. those that are easily accessible for immuno-monitoring and could help predict vaccines efficacy.

Genomic Circuitry Underlying Immunological Response to Pediatric Acute Respiratory Infection

“…Moreover, ISG expression was distinct in the younger pediatric participants. Specifically, the upregulated ISGs in acute IFV, well appreciated in mouse (Brinza et al, 2016) and human data (Mejias et al, 2013), characterized the dominant component of the older patients, as expected. However, in younger participants, there was only moderate ISG upregulation with less involvement of STAT1 and STAT2 .…”

“…Moreover, because IFV does not cause viremia and peripheral CD8 T cells are not directly infected by IFV, the alterations in CD8 T cell transcriptional networks are more likely due to conditioning of the global CD8 T cell population by early innate antiviral events. The prominent signature of IFN signaling in circulating CD8 T cells in IFV infection is expected (Brinza et al, 2016) and reveals both the systemic impact of IFN circuits in respiratory IFV infection and the ability of circulating CD8 T cells to sense and respond to this key signal of viral infection. In contrast, the downregulated genes and pathways including an NFκB-focused hub was unexpected.…”

Antigen-Induced but Not Innate Memory CD8 T Cells Express NKG2D and Are Recruited to the Lung Parenchyma upon Viral Infection

“…Thus, long-term protection of the lung relies on the recruitment of secondary memory cells stored in lymphoid tissues. Indeed, following infection of the lung, inflammation rapidly induces the recruitment of memory cells independently of their Ag specificity (43,44,49), although pathogen-specific spleen memory T cells also rapidly gain access to the tissue (2).…”

“…Protection against intracellular pathogens or tumor-derived Ag is conferred in part by Ag-induced (AI) memory CD8 T cells. Indeed, AI memory CD8 T cells have improved functional properties compared with naive cells, making them more potent to rapidly eliminate infected cells upon reinfection (1,2). These AI memory cells are found in secondary lymphoid organs, but a subset of them, the tissue-resident memory cells (TRM), settles within nonlymphoid tissues where they provide increased protection against secondary pathogen infections (3,4).…”

Порівняльна Анатомо-Імуногістохімічна Характеристика Селезінки Представників Класів Птахи І Ссавці

“…Це зумов лено важливими і численними функціями, які вона виконує: фільтраційною, очисною, імунною, кровотворною, депонувальною, крім того, займає центральне місце в контролі антигенного складу крові й початку імунної відповіді [1,2]. Лімфоїд ній тканині селезінки, як й імунній системі в ці лому, властива унікальна здатність розпізнавати антигени і специфічно реагувати на них [2][3][4][5][6]. Сучасні імуногістохімічні методи дозволяють з'ясувати стромальні взаємозв'язки в органі [7] та проводити імунофенотипування лімфоцитів при патологічних станах організму і впливі різних чинників [4,8].…”