CXCR6 identifies a putative population of retained human lung T cells characterised by co-expression of activation markers

Abstract

Expressions of activation markers have been described on the surface of T cells in the blood and the lung in both health and disease. We have studied the distribution of activation markers on human lung T cells and have found that only certain populations exist. Importantly, the presence or absence of some markers appears to predict those of others, in particular cells which express CD103 also express CD49a and CD69, whereas cells which do not express CD69 also do not express CD49a or CD103.In view of the paucity of activation marker expression in the peripheral blood, we have hypothesised that these CD69+, CD49a+, and CD103+ (triple positive) cells are retained in the lung, possess effector function (IFNγ secretion) and express particular chemokine receptors which allow them to be maintained in this environment.We have found that the ability of the triple negative cells to secrete IFNγ is significantly less than the triple positive cells, suggesting that the expression of activation markers can highlight a highly specialised effector cell. We have studied the expression of 14 chemokine receptors and have found that the most striking difference between the triple negative cells and the triple positive cells is the expression of CXCR6 with 12.8±9.8% of triple negative cells expressing CXCR6 compared to 89.5 ±5.5% of triple positive cells.We propose therefore that CXCR6 may play an important role in the retention of T cells within the lung.

CD8+ T cells with an intraepithelial phenotype upregulate cytotoxic function upon influenza infection in human lung

“…Immunohistochemistry confirmed that most lung CD103 + CD3 + CD8 + T cells were indeed located intraepithelially above the basement membrane of the small airways ( Figure 1C), as was previously published (13)(14)(15)(16).…”

“…In addition, many FLUspecific cells in the lung expressed VLA-1 (α 1 β 1 integrin) (Figure 2, B and C), which in mice has been shown to be responsible for retaining influenza-specific memory CD8 + T cells in the lung by binding to the type IV collagen-rich basement membrane (20)(21)(22). Although VLA-1 is expressed mainly by CD103 + CD8 + lung T cells (15) (Supplemental Figure 3), both CD103 + and CD103 -FLU-specific lung T cells expressed VLA-1. Thereby, the vast majority of FLU-specific T cells (mean of 87%) expressed at least 1 of these 2 integrins (Supplemental Figure 2B), whereas this was only the case for the minority of EBV-and CMV-specific T cells.…”

“…Intraepithelial CD8 + T cells express αEβ7 integrin, which binds to epithelial cadherin (E-cadherin), expressed by the epithelial cells (11)(12)(13)(14)(15)(16). This interaction retains the IELs in the vicinity of the epithelium (17)(18)(19).…”

IL-2–Controlled Expression of Multiple T Cell Trafficking Genes and Th2 Cytokines in the Regulatory T Cell-Deficient Scurfy Mice: Implication to Multiorgan Inflammation and Control of Skin and Lung Inflammation

“…The expression of CCR8 and its ligand CCL1 has been associated with allergic lung and skin diseases (50, 52). CXCR6 can be induced by IL-2 on the peripheral blood T cells, whereas its ligand CXCL16 is constitutively expressed in bronchial epithelium and is highly upregulated in skin during psoriasis (53–55). Expression of CCR1 is upregulated on T cells during allergic conditions, and its ligand CCL8 is also chemotactic for eosinophils, basophils, and mast cells in allergy and asthma (42).…”

CXCR6 Is a Marker for Protective Antigen-Specific Cells in the Lungs after Intranasal Immunization against Mycobacterium tuberculosis

“…In humans, CXCL16, the only known ligand for CXCR6, is expressed constitutively in lung epithelia, may be responsible for the long-term retention of CD3 ϩ T cells in lungs, and may also play a role in chronic obstructive pulmonary disease (9,10,15,34). Because CXCR6-CXCL16 was the only chemokine receptor-chemokine pair shown by our microarray analysis to be upregulated in the lungs of protected, i.n.…”