Showing papers by "Francis R. Carbone published in 2013"
TL;DR: It is found that CD103+CD8+ TRM cells developed in the skin from epithelium-infiltrating precursor cells that lacked expression of the effector-cell marker KLRG1.
Abstract: Tissue-resident memory T cells (T(RM) cells) provide superior protection against infection in extralymphoid tissues. Here we found that CD103(+)CD8(+) T(RM) cells developed in the skin from epithelium-infiltrating precursor cells that lacked expression of the effector-cell marker KLRG1. A combination of entry into the epithelium plus local signaling by interleukin 15 (IL-15) and transforming growth factor-β (TGF-β) was required for the formation of these long-lived memory cells. Notably, differentiation into T(RM) cells resulted in the progressive acquisition of a unique transcriptional profile that differed from that of circulating memory cells and other types of T cells that permanently reside in skin epithelium. We provide a comprehensive molecular framework for the local differentiation of a distinct peripheral population of memory cells that forms a first-line immunological defense system in barrier tissues.
996 citations
TL;DR: Evidence for tissue-resident memory T cell (TRM) is reviewed, a relatively new player is highlighted, and the potential differences between the migratory patterns of CD4(+) and CD8(+) T cells are emphasized.
Abstract: Tissues such as the skin and mucosae are frequently exposed to microbial pathogens. Infectious agents must be quickly and efficiently controlled by our immune system, but the low frequency of naive T cells specific for any one pathogen means dependence on primary responses initiated in draining lymph nodes, often allowing time for serious infection to develop. These responses imprint effectors with the capacity to home to infected tissues; this process, combined with inflammatory signals, ensures the effective targeting of primary immunity. Upon vaccination or previous pathogen exposure, increased pathogen-specific T cell numbers together with altered migratory patterns of memory T cells can greatly improve immune efficacy, ensuring infections are prevented or at least remain subclinical. Until recently, memory T cell populations were considered to comprise central memory T cells (TCM), which are restricted to the secondary lymphoid tissues and blood, and effector memory T cells (TEM), which broadly migrate between peripheral tissues, the blood, and the spleen. Here we review evidence for these two memory populations, highlight a relatively new player, the tissue-resident memory T cell (TRM), and emphasize the potential differences between the migratory patterns of CD4(+) and CD8(+) T cells. This new understanding raises important considerations for vaccine design and for the measurement of immune parameters critical to the control of infectious disease, autoimmunity, and cancer.
695 citations
TL;DR: Many of the innate and adaptive immune cell types associated with the skin are outlined, focusing on the steady state in mice and men, and include a broad update of dendritic cell function and T cell surveillance.
Abstract: The skin is a highly complex organ interspersed with a variety of smaller organ-like structures and a plethora of cell types that together perform essential functions such as physical sensing, temperature control, barrier maintenance and immunity. In this Review, we outline many of the innate and adaptive immune cell types associated with the skin, focusing on the steady state in mice and men, and include a broad update of dendritic cell function and T cell surveillance.
321 citations
TL;DR: T tissue-resident memory T (T(RM)) cells are phenotypically distinct from T(EM) cells, persist in elevated numbers in areas involved in prior infection and have been implicated in various immune phenomena, such as the control of persisting infections and immune disorders in fixed regions of the body.
88 citations
TL;DR: An appreciation of the T cells in the non-lymphoid memory pool and their relationship to those in the circulation is an important step in understanding how to generate and exploit effective peripheral immunity for the purpose of infection control.
57 citations
TL;DR: This analysis identified one D(b)-restricted peptide sequence within DsRed (SSLQDGCFI) that acted as an epitope for B6 target lysis and cautions against using this fluorochrome, as well as several others containing the immunogenic sequence, in adoptive transfer studies where rejection is not desirable.
12 citations