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

Abstract

The human lung T cell compartment contains many CD8 + T cells specific for respiratory viruses, suggesting that the lung is protected from recurring respiratory infections by a resident T cell pool. The entry site for respiratory viruses is the epithelium, in which a subset of lung CD8 + T cells expressing CD103 (αE integrin) resides. Here, we determined the specificity and function of CD103 + CD8 + T cells in protecting human lung against viral infection. Mononuclear cells were isolated from human blood and lung resection samples. Variable numbers of CD103 + CD8 + T cells were retrieved from the lung tissue. Interestingly, expression of CD103 was seen only in lung CD8 + T cells specific for influenza but not in those specific for EBV or CMV. CD103 + and influenza-reactive cells preferentially expressed NKG2A, an inhibitor of CD8 + T cell cytotoxic function. In contrast to CD103 -CD8 + T cells, most CD103 + CD8 + cells did not contain perforin or granzyme B. However, they could quickly upregulate these cytotoxic mediators when exposed to a type I IFN milieu or via contact with their specific antigen. This mechanism may provide a rapid and efficient response to influenza infection, without inducing cytotoxic damage to the delicate epithelial barrier.

CD8+CD103+ Tumor–Infiltrating Lymphocytes Are Tumor-Specific Tissue-Resident Memory T Cells and a Prognostic Factor for Survival in Lung Cancer Patients

“…Consistently, CD103 was maintained on vesicular stomatitis virus-specific CD8 + T cells only as long as the Ag was present (21). Moreover, influenza virus-specific T lymphocytes, but not EBV-and CMV-specific T lymphocytes, express the integrin, further emphasizing that a sufficient Ag amount is needed to maintain CD103 expression (24). The present study also suggests that CD103 is involved, at least in part, in recruitment of CD8 + T cells in lung tumor islets and provides evidence that a high density of CD103 + TIL is associated with early stage NSCLC patient survival.…”

“…T RM T cells are highly activated T lymphocytes that reside within a variety of peripheral tissues, including intestine (17,20), brain (21), skin (22,23), and lung (24), and provide early responses to viral reinfection (25). Accumulating evidence indicates that TGF-b1 plays an essential role in the formation and maintenance of T RM T cells, at least in part via induction of CD103 and CD69.…”

“…Thus, TGF-b1, considered as an immunosuppressive cytokine, can control immune responses to viral infections and tumors via induction of CD103 and formation of CD8 + CD103 + T RM T cells. The CD103 2 lymphocytes observed in several NSCLC tumors might represent either nonspecific T cells passing through the lung tumor lesion or recently recruited tumor- which CD103 is expressed on CD8 + T cells specific to influenza virus in the lung (24), EBV in the tonsil (32), and cancer testis Ag NY-ESO-1 in ovarian cancer (9). In the latter and present studies, CD103 + T cells expressed high levels of PD-1, which has been defined as a biomarker of tumor-specific T cells (33).…”

Tissue-Resident Memory T Cells and Fixed Immune Surveillance in Nonlymphoid Organs

“…T RM -like cells have been proposed to exist upon resolution of skin infection with HSV (49,50), and the presence of these cells correlates with enhanced virus control (61). T RM cells also were found in human lung (59), with influenza-specific CD8 + T cells localizing to the CD103 + intraepithelial lymphocyte fraction (62). Fixed drug eruption in skin also was linked with intraepithelial CD8 + CD103 + T cells (63).…”

Important Factors of the Inflammatory Process in the O Ropharynx and Optimal Treatment Regimes Selection

“…Перфорин встраивается в мембрану пораженной клетки и образует там поры. С помощью эндоцитоза клетка старается их ликвидиро-вать и при этом захватывает гранзим, который индуциру-ет ее апоптоз и конечную гибель [7]. Помимо регуляторов клеточного и гуморального иммунитета с их противови-русными и цитотоксическими свойствами, к процессу воспаления подключены про-и противовоспалительные цитокины, которые их активируют.…”