CD49a Identifies Polyfunctional Memory CD8 T Cell Subsets that Persist in the Lungs After Influenza Infection

Reilly, Emma; Sportiello, Mike; Emo, Kris Lambert; Amitrano, Andrea M.; Jha, Rakshanda; Kumar, Ashwin B. R.; Laniewski, Nathan; Yang, Hongmei; Kim, Min‐Soo; Topham, David J.

doi:10.3389/fimmu.2021.728669

Cited by 24 publications

(27 citation statements)

References 64 publications

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“…All children with active TB were culture negative and symptom free at the end of ATT. The demographic and epidemiological data have been previously reported [ 14 ].…”

Section: Methodsmentioning

confidence: 99%

Plasma chemokines as immune biomarkers for diagnosis of pediatric tuberculosis

et al. 2021

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Background Diagnosing tuberculosis (TB) in children is challenging due to paucibacillary disease, and lack of ability for microbiologic confirmation. Hence, we measured the plasma chemokines as biomarkers for diagnosis of pediatric tuberculosis. Methods We conducted a prospective case control study using children with confirmed, unconfirmed and unlikely TB. Multiplex assay was performed to examine the plasma CC and CXC levels of chemokines. Results Baseline levels of CCL1, CCL3, CXCL1, CXCL2 and CXCL10 were significantly higher in active TB (confirmed TB and unconfirmed TB) in comparison to unlikely TB children. Receiver operating characteristics curve analysis revealed that CCL1, CXCL1 and CXCL10 could act as biomarkers distinguishing confirmed or unconfirmed TB from unlikely TB with the sensitivity and specificity of more than 80%. In addition, combiROC exhibited more than 90% sensitivity and specificity in distinguishing confirmed and unconfirmed TB from unlikely TB. Finally, classification and regression tree models also offered more than 90% sensitivity and specificity for CCL1 with a cutoff value of 28 pg/ml, which clearly classify active TB from unlikely TB. The levels of CCL1, CXCL1, CXCL2 and CXCL10 exhibited a significant reduction following anti-TB treatment. Conclusion Thus, a baseline chemokine signature of CCL1/CXCL1/CXCL10 could serve as an accurate biomarker for the diagnosis of pediatric tuberculosis.

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“…All children with active TB were culture negative and symptom free at the end of ATT. The demographic and epidemiological data have been previously reported [ 14 ].…”

Section: Methodsmentioning

confidence: 99%

Plasma chemokines as immune biomarkers for diagnosis of pediatric tuberculosis

et al. 2021

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“…CD8 + T RM cells are defined by co-expression of CD69 and integrin α E sub-unit (CD103) [7]. In addition, in the lungs of humans and mice, T RM cells can also express integrin α 1 sub-unit (CD49a) and CCL16 chemokine receptor CXCR6 [8][9][10] but are heterogeneous and exhibit different expression levels of other surface markers [11,12]. In the lungs, T RM cells are important for the control of viral respiratory infections, as well as being the main drivers of heterosubtypic immunity to influenza A (IAV) infection [13][14][15][16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Type I interferons and MAVS signaling are necessary for tissue resident memory CD8+ T cell responses to RSV infection

et al. 2022

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Respiratory syncytial virus (RSV) can cause bronchiolitis and viral pneumonia in young children and the elderly. Lack of vaccines and recurrence of RSV infection indicate the difficulty in eliciting protective memory immune responses. Tissue resident memory T cells (TRM) can confer protection from pathogen re-infection and, in human experimental RSV infection, the presence of lung CD8+ TRM cells correlates with a better outcome. However, the requirements for generating and maintaining lung TRM cells during RSV infection are not fully understood. Here, we use mouse models to assess the impact of innate immune response determinants in the generation and subsequent expansion of the TRM cell pool during RSV infection. We show that CD8+ TRM cells expand independently from systemic CD8+ T cells after RSV re-infection. Re-infected MAVS and MyD88/TRIF deficient mice, lacking key components involved in innate immune recognition of RSV and induction of type I interferons (IFN-α/β), display impaired expansion of CD8+ TRM cells and reduction in antigen specific production of granzyme B and IFN-γ. IFN-α treatment of MAVS deficient mice during primary RSV infection restored TRM cell expansion upon re-challenge but failed to recover TRM cell functionality. Our data reveal how innate immunity, including the axis controlling type I IFN induction, instructs and regulates CD8+ TRM cell responses to RSV infection, suggesting possible mechanisms for therapeutic intervention.

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“…CD49a and CD69 play well-established roles in TRM cell survival, trafficking, and retention, while the role of CD103 on the lung TRM cells is less understood, although it has been suggested to promote epithelial adherence ( 87 ). In particular, recent work has demonstrated that CD49a is a common marker of TRM cell cytolytic activity irrespective of CD103 expression ( 88 ). In line with these reports, we observed that Blimp-1 hi TRM cells from lung allografts with BOS expressed high levels of CD49a and Grzmb readily killed pulmonary epithelial cells.…”

Section: Discussionmentioning

confidence: 99%

Reprogramming alveolar macrophage responses to TGF-β reveals CCR2+ monocyte activity that promotes bronchiolitis obliterans syndrome

Liu¹,

Liao²,

Zhu³

et al. 2022

Journal of Clinical Investigation

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Bronchiolitis obliterans syndrome (BOS) is a major impediment to lung transplant survival and is generally resistant to medical therapy. Extracorporeal photophoresis (ECP) is an immunomodulatory therapy that shows promise in stabilizing BOS patients, but its mechanisms of action are unclear. In a mouse lung transplant model, we show that ECP blunts alloimmune responses and inhibits BOS through lowering airway TGF-β bioavailability without altering its expression. Surprisingly, ECP-treated leukocytes were primarily engulfed by alveolar macrophages (AMs), which were reprogrammed to become less responsive to TGF-β and reduce TGF-β bioavailability through secretion of the TGF-β antagonist decorin. In untreated recipients, high airway TGF-β activity stimulated AMs to express CCL2, leading to CCR2 + monocyte-driven BOS development. Moreover, we found TGF-β receptor 2–dependent differentiation of CCR2 + monocytes was required for the generation of monocyte-derived AMs, which in turn promoted BOS by expanding tissue-resident memory CD8 + T cells that inflicted airway injury through Blimp-1–mediated granzyme B expression. Thus, through studying the effects of ECP, we have identified an AM functional plasticity that controls a TGF-β–dependent network that couples CCR2 + monocyte recruitment and differentiation to alloimmunity and BOS.

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CD49a Identifies Polyfunctional Memory CD8 T Cell Subsets that Persist in the Lungs After Influenza Infection

Cited by 24 publications

References 64 publications

Plasma chemokines as immune biomarkers for diagnosis of pediatric tuberculosis

Plasma chemokines as immune biomarkers for diagnosis of pediatric tuberculosis

Type I interferons and MAVS signaling are necessary for tissue resident memory CD8+ T cell responses to RSV infection

Reprogramming alveolar macrophage responses to TGF-β reveals CCR2+ monocyte activity that promotes bronchiolitis obliterans syndrome

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