Cutting Edge: Gut Microenvironment Promotes Differentiation of a Unique Memory CD8 T Cell Population

Masopust, David; Vezys, Vaiva; Wherry, E. John; Barber, Daniel L.; Ahmed, Rafi

doi:10.4049/jimmunol.176.4.2079

Cited by 320 publications

(378 citation statements)

References 35 publications

(38 reference statements)

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“…Our article also shows that systemic CD8 ϩ T lymphocytes up-regulate mucosal homing markers and rapidly migrate to mucosal surfaces following intramuscular immunization, providing a mechanism for the capacity of systemic vaccines to elicit mucosal cellular immune memory. These findings are consistent with previous observations regarding the phenotypic plasticity of systemic and mucosal CD8 ϩ T lymphocytes (12) and their ability to be dynamically reprogrammed with respect to tissue homing capacity after initial priming in peripheral lymph nodes (13). Thus, it is clear that mucosal immunization strategies are not necessarily required for inducing mucosal immunity.…”

Section: Letters To the Editor Letters To The Editorsupporting

confidence: 81%

Comment on “Trafficking of Antigen-Specific CD8+ T Lymphocytes to Mucosal Surfaces following Intramuscular Vaccination”

Belyakov¹,

Ahlers²

2009

The Journal of Immunology

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Section: Letters To the Editor Letters To The Editorsupporting

confidence: 81%

Comment on “Trafficking of Antigen-Specific CD8+ T Lymphocytes to Mucosal Surfaces following Intramuscular Vaccination”

Belyakov¹,

Ahlers²

2009

The Journal of Immunology

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“…S3A). The high levels of CD69 and CD103 in SMG P14 memory T cells were reminiscent of the previously described phenotype of P14 memory T cells isolated from the IEL compartment (7). In contrast to P14 memory T cells in SMG, P14 IEL were negative for Ly6C but could also be stained with E-cadherin-specific mAb (Fig.…”

Section: Resultsmentioning

confidence: 76%

“…Virus-specific CD8 T RM cells have been described in sensory ganglia, skin, brain, and intestinal mucosa (4-11). Common features of differently localized T RM cells are the expressions of the α E β 7 integrin CD103 and of CD69 (4,5,7,9). Submandibular glands (SMG) are accessory organs of the oral mucosa and well-characterized effector sites of the mucosal IgA response (12, 13).…”

mentioning

confidence: 99%

E-cadherin promotes accumulation of a unique memory CD8 T-cell population in murine salivary glands

Hofmann

Pircher

2011

Proc. Natl. Acad. Sci. U.S.A.

146

178

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The salivary glands are important effector sites for IgA-mediated humoral immunity to protect oral surfaces. Within murine submandibular glands (SMG), we identified a memory CD8 T-cell population that exhibited a unique cell-surface phenotype distinct from memory CD8 T cells in spleen but similar to memory T cells resident in the intraepithelial lymphocyte compartment of the intestinal mucosa. In mice immune to lymphocytic choriomeningitis virus (LCMV) or vesicular stomatitis virus (VSV), virus-specific memory CD8 T cells with this unusual phenotype were present in SMG at remarkably high frequencies. LCMV-specific memory CD8 T cells in SMG showed potent functional activities in vivo, including cytokine-induced bystander proliferation, antigen-triggered IFNγ production, and viral clearance. Adoptive transfer experiments further revealed that the capacity to accumulate in SMG decreased during CD8 Tcell differentiation and that SMG CD8 T cells were poorly replenished from the circulation, indicating that they were tissue-resident. Moreover, they preferentially relocalized within their tissue of origin after adoptive transfer and antigen rechallenge, thus revealing an imprinted differentiation status. Accumulation of memory CD8 T cells within SMG did not require local antigen presentation but was promoted by the epithelial differentiation molecule E-cadherin intrinsically expressed by these CD8 T cells. This finding extends the epithelial-restricted function of E-cadherin to an impact on lymphocyte accumulation within epithelial tissues.epithelial tissues | viral infections T he establishment of a multilayered memory T-cell system provides high flexibility to combat reinfections with different pathogens. Central memory T cells (T CM ) build up a long-lasting pool of rapidly replicating cells in secondary lymphoid organs whereas effector memory T cells (T EM ) patrolling blood, spleen, and nonlymphoid tissues are crucial to fighting incoming infections by immediate effector functions (1, 2). Parabiosis experiments, however, revealed that entry of blood-borne memory T cells into brain and gut lamina propria is restricted (3). Moreover, recent studies have suggested a prominent role of tissueresident memory T cells (T RM ) in providing local protection (4). Virus-specific CD8 T RM cells have been described in sensory ganglia, skin, brain, and intestinal mucosa (4-11). Common features of differently localized T RM cells are the expressions of the α E β 7 integrin CD103 and of CD69 (4,5,7,9). Submandibular glands (SMG) are accessory organs of the oral mucosa and well-characterized effector sites of the mucosal IgA response (12, 13). In addition to B cells, SMG also accommodate αβ and γδ T cells, NK cells, and other innate immune cell populations (13, 14). The glandular tissue further represents an important target organ for cytomegalovirus infections and for autoimmune reactions (15, 16). As SMG are exocrine epithelial tissues, the epithelial differentiation molecule E-cadherin is highly expressed in these organs. E-cadh...

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“…Although cells of this phenotype display a limited lifespan and proliferative capacity compared with KLRG1 lo IL-7R hi memory CD8 + T cells in circulation, they can offer enhanced protection to some types of pathogens due to elevated cytotoxic activity (Jabbari and Harty, 2006;Olson et al, 2013) and, interestingly, are more prominently observed after serial infections (Masopust et al, 2006;Wirth et al, 2010;Joshi et al, 2011;Fraser et al, 2013;Olson et al, 2013). Thus, it will be important to determine if sustained ZEB2 expression is necessary for maintenance of this population of T EM cells.…”

Section: Discussionmentioning

confidence: 99%

The transcription factors ZEB2 and T-bet cooperate to program cytotoxic T cell terminal differentiation in response to LCMV viral infection

Dominguez¹,

Guan²,

Marshall³

et al. 2015

J Cell Biol

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Cutting Edge: Gut Microenvironment Promotes Differentiation of a Unique Memory CD8 T Cell Population

Cited by 320 publications

References 35 publications

Comment on “Trafficking of Antigen-Specific CD8+ T Lymphocytes to Mucosal Surfaces following Intramuscular Vaccination”

Comment on “Trafficking of Antigen-Specific CD8+ T Lymphocytes to Mucosal Surfaces following Intramuscular Vaccination”

E-cadherin promotes accumulation of a unique memory CD8 T-cell population in murine salivary glands

The transcription factors ZEB2 and T-bet cooperate to program cytotoxic T cell terminal differentiation in response to LCMV viral infection

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