Tissue Distribution of Memory T and B Cells in Rhesus Monkeys following Influenza A Infection

Abstract

Studies of influenza-specific immune responses in humans have largely assessed systemic responses involving serum Ab and peripheral blood T cell responses. However, recent evidence indicates that tissue-resident memory T (TRM) cells play an important role in local murine intrapulmonary immunity. Rhesus monkeys were pulmonary exposed to 2009 pandemic H1N1 virus at days 0 and 28 and immune responses in different tissue compartments were measured. All animals were asymptomatic postinfection. Although only minimal memory immune responses were detected in peripheral blood, a high frequency of influenza nucleoprotein–specific memory T cells was detected in the lung at the “contraction phase,” 49–58 d after second virus inoculation. A substantial proportion of lung nucleoprotein-specific memory CD8+ T cells expressed CD103 and CD69, phenotypic markers of TRM cells. Lung CD103+ and CD103- memory CD8+ T cells expressed similar levels of IFN-γ and IL-2. Unlike memory T cells, spontaneous Ab secreting cells and memory B cells specific to influenza hemagglutinin were primarily observed in the mediastinal lymph nodes. Little difference in systemic and local immune responses against influenza was observed between young adult (6–8 y) and old animals (18–28 y). Using a nonhuman primate model, we revealed substantial induction of local T and B cell responses following 2009 pandemic H1N1 infection. Our study identified a subset of influenza-specific lung memory T cells characterized as TRM cells in rhesus monkeys. The rhesus monkey model may be useful to explore the role of TRM cells in local tissue protective immunity after rechallenge and vaccination.

A Human-Immune-System (HIS) humanized mouse model (DRAGA: HLA-A2. HLA-DR4. Rag1 KO.IL-2Rγc KO. NOD) for COVID-19

“…5). Interestingly, some of the human CD3 + T-cell infiltrates appeared to be fairly organized, such those described in the epithelial lung niches of severely-infected mice and humans with influenza viruses [60][61][62][63][64] (Fig. 5E).…”

Memory T cell subsets in healthy gingiva and periodontitis tissues

“…Measurement of IL‐17 and IFN‐γ production in recirculating versus gingiva‐resident memory T cells based on CD69 expression was not possible because in vitro stimulation with SEB leads to CD69 expression on most T cells . We next compared the cytokine response between the memory T cell CD103 + and CD103 − subsets.…”

“…Measurement of IL-17 and IFN-production in recirculating versus gingiva-resident memory T cells based on CD69 expression was not possible because in vitro stimulation with SEB leads to CD69 expression on most T cells. 29 We next compared the cytokine response between the memory T cell CD103 + and CD103 − subsets. We found that the frequency of CD4 + CD103 + memory T cells that produced IFN-was 4.4-fold higher than that of CD4 + CD103 − memory T cells however, the differences did not reach statistical significance (12.87% ± 4.82% versus 2.92% ± 1.55%; P = 0.06) ( Figure 5B).…”

Fueling influenza and the immune response: Implications for metabolic reprogramming during influenza infection and immunometabolism

“…IgG-secreting plasma cells localized to the lung and peak at 2 weeks, finally resolving the infection. 98,99 Organisms lacking adaptive immunity were shown to have enhanced resistance to subsequent infections (trained immunity). Innate trained immunity occurs in human monocytes and MØ; mTOR/Akt/PI3K-regulated metabolic reprogramming, including increased glutamine metabolism, a shift from OXPHOS-to-aerobic glycolysis, and cholesterol synthesis contribute to this process.…”