E 7 (CD103) Expression Identifies a Highly Active, Tonsil-Resident Effector-Memory CTL Population

Partners AIDS Research Center, Massachusetts General Hospital, Boston 02129, USA.
The Journal of Immunology (Impact Factor: 4.92). 11/2005; 175(7):4355-62. DOI: 10.4049/jimmunol.175.7.4355
Source: PubMed


The characterization of antiviral CTL responses has largely been limited to assessing Ag-specific immune responses in the peripheral blood. Consequently, there is an incomplete understanding of the cellular immune responses at mucosal sites where many viruses enter and initially replicate and how the Ag specificity and activation status of CTL derived from these mucosal sites may differ from that of blood-derived CTL. In this study, we show that EBV-specific CTL responses in the tonsils are of comparable specificity and breadth but of a significantly higher magnitude compared with responses in the peripheral blood. EBV-specific, tonsil-resident, but not PBMC-derived, T cells expressed the integrin/activation marker CD103 (alphaEbeta7), consistent with the detection of its ligand, E-cadherin, on tonsillar squamous cells. These CD8-positive, CD103-positive, tonsil-derived CTL were largely CCR7- and CD45RA- negative effector-memory cells and responded to lower Ag concentrations in in vitro assays than their CD103-negative PBMC-derived counterparts. Thus, EBV-specific CTL in the tonsil, a crucial site for EBV entry and replication, are of greater magnitude and phenotypically distinct from CTL in the peripheral blood and may be important for effective control of this orally transmitted virus.

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Available from: Christian Brander, Sep 12, 2014
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    • "Understanding the receptors, chemokines, and other factors that influence formation of a TRM population in non-lymphoid tissues is an area of active research. Intra-epithelial lymphocytes (IELs), the TRM cells in the gut epithelium, downregulate expression of homing receptors α4β7 and CCR9 and upregulate CD69 and CD103 to establish residence (89, 94). Decrease in the expression of KLF2, the transcriptional activator of the gene that codes for S1PR1 was recently shown to be important for establishment of resident memory CD8+ T cells (95) in non-lymphoid tissues. "
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    • "Other examples of T RM cells in humans include influenza virus-specific CD8 + CD103 + T cells that persist in the alveolar epithelium of the lungs (Piet et al., 2011), as well as virusspecific CD8 + memory T cells that are preferentially retained in close proximity to the epidermis and peripheral nerves following HSV-2 infection in vaginal skin (Zhu et al., 2007, 2009). In addition, Epstein-Barr virus-specific CD8 + CD103 + T cells have been detected at high frequencies in the tonsils of persistently infected individuals (Hislop et al., 2005; Woodberry et al., 2005). Collectively, these studies strongly suggest that permanently tissue-resident T cells equivalent to the CD8 + CD103 + T RM cells defined in mice, also exist in humans. "
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