Tissue Exit: a Novel Control Point in the Accumulation of Antigen-Specific CD8 T Cells in the Influenza A Virus-Infected Lung

Jennrich, Silke; Lee, Michael H.; Lynn, Rachel C.; Dewberry, Kristofer; Debes, Gudrun F.

doi:10.1128/jvi.07025-11

Cited by 38 publications

(36 citation statements)

References 58 publications

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“…1). This is in agreement with data demonstrating that upon antigenic stimulation in situ , virus-specific CD8 + T cells decrease their egress from the lung during influenza virus infection (10) and/or develop into long-term T RM cells in the vesicular stomatitis virus-infected brain (31). As T cell entry into tissues is independent of antigen specificity (32), enhancing the retention of antigen-specific T cells by decreased egress from sites of inflammation and infection ensures continued T cell effector functions, while allowing bystander T cells to egress and redistribute.…”

Section: Discussionsupporting

confidence: 92%

“…Lymphocytes were isolated from lymph nodes and spleens by passage through 40 μm cell strainers (BD Biosciences), as described (10). Red blood cells were lysed with 160 mM ammonium chloride and cells washed in RPMI 1640 with 10% fetal bovine serum.…”

Section: Methodsmentioning

confidence: 99%

“…Given the large number of lymphocytes, including pro-inflammatory Th1 and Th17 cells, that egress from chronically inflamed sites (8, 9); T cell egress potentially determines effector T cell accumulation and their downstream effector functions in situ . During inflammation and infection, the CCR7-CCL21 receptor-ligand pair guides T cells out of affected tissues via afferent lymph (5, 9, 10), and CCR7 deficiency promotes the development of long-term tissue-resident memory T cells (T RM ) 4 key to site-specific immunity (11). However, inflammation also facilitates CCR7-independent T cell tissue egress (9, 12) with contributions from additional chemoattractants, such as sphingosine-1 phosphate (9, 13).…”

Section: Introductionmentioning

confidence: 99%

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Effector T Cell Egress via Afferent Lymph Modulates Local Tissue Inflammation

Gómez

Diehl

Crosby

et al. 2015

The Journal of Immunology

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Memory/effector T cells recirculate through extralymphoid tissues by entering from blood and egressing via afferent lymph. While T cell entry into effector sites is key to inflammation, the relevance of T cell egress to this process is unknown. Here we found that antigen recognition at the effector site reduced the tissue egress of pro-inflammatory Th1 cells in a mouse model of delayed hypersensitivity. Transgenic expression of ‘tissue exit receptor’ CCR7 enhanced lymphatic egress of antigen-sequestered Th1 cells from the inflamed site and ameliorated inflammation. In contrast, lack of CCR7 on Th1 cells diminished their tissue egress while enhancing inflammation. Lymph-borne Th1 and Th17 cells draining the inflamed skin of sheep migrated toward the CCR7 ligand CCL21, suggesting the CCR7-CCL21 axis as a physiological target in regulating inflammation. In conclusion, exit receptors can be targeted to modulate T cell dwell time and inflammation at effector sites, revealing T cell tissue egress as a novel control point of inflammation.

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Section: Discussionsupporting

confidence: 92%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effector T Cell Egress via Afferent Lymph Modulates Local Tissue Inflammation

Gómez

Diehl

Crosby

et al. 2015

The Journal of Immunology

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“…Exiting from tissues requires that CD8 + T cells enter lymphatic vessels that will passively carry them to the draining lymph node and eventually back to the circulation. Like dendritic cells, CD8 + T cells utilize CCR7 to efficiently enter lymphatic vessels before transiting to the draining lymph nodes [79-81]. It has also been reported that S1PR1 also guides CD8 + T cells toward afferent lymphatic vessels [82].…”

Section: Trafficking Of Recently Activated Effector Cd8+ T Cellsmentioning

confidence: 99%

Molecular mechanisms of CD8+ T cell trafficking and localization

Nolz

2015

Cell. Mol. Life Sci.

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Cytotoxic CD8+ T cells are potent mediators of host protection against disease due to their ability to directly kill cells infected with intracellular pathogens and produce inflammatory cytokines at the site of infection. To fully achieve this objective, naïve CD8+ T cells must be able to survey the entire body for the presence of foreign or “non-self” antigen that is delivered to draining lymph nodes following infection or tissue injury. Once activated, CD8+ T cells undergo many rounds of cell division, acquire effector functions, and are no longer restricted to the circulation and lymphoid compartments like their naïve counterparts, but rather are drawn to inflamed tissues in order to combat infection. As CD8+ T cells transition from naïve to effector to memory populations, this is accompanied by dynamic changes in the expression of adhesion molecules and chemokine receptors that ultimately dictate their localization in vivo. Thus, an understanding of the molecular mechanisms regulating CD8+ T cell trafficking and localization are critical for vaccine design, control of infectious diseases, treatment of autoimmune disorders, and cancer immunotherapy.

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“…124,125 During influenza virus infection, the exit of effector CD8 T cells from the lungs is facilitated by the CCR7 ligand, CCL21, which is expressed in lymphatic endothelial cells during infection. 126 Once CCR7 is downregulated, the rate of T-cell migration from the lung tissues to the mediastinal LN diminishes. In contrast, forced expression of CCR7 results in more rapid exit of effector T cells from the lung, 122 whereas in another model CCR7 deficiency prevents tissue-resident lymphocytes from leaving the skin.…”

Section: Retention and Exit Of Pathogen-specific T Cells From The Mucmentioning

confidence: 99%

Guarding the perimeter: protection of the mucosa by tissue-resident memory T cells

Cauley

Lefrançois

2013

Mucosal Immunology

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Mucosal tissues are continually bombarded with infectious agents seeking to gain entry into the body. The absence of a tough physical exterior layer surrounding these tissues creates a unique challenge for the immune system, which manages to provide broad protection against a plethora of different organisms with the aid of special adaptations that augment immunity at these vulnerable sites. For example, specialized populations of memory T lymphocytes reside at initial sites of pathogen entry into the body, where they provide an important protective barrier. Similar anatomically confined populations of pathogen-specific CD8 T cells can be found near the outer margins of the body following recovery from a variety of local infections, where they share very similar phenotypic characteristics. How these tissue-resident T cells are retained in a single anatomic location where they can promote immunity is beginning to be defined. Here, we will review current knowledge of the mechanisms that help establish and maintain these regional lymphocytes in the mucosal tissues and discuss relevant data that enhance our understanding of the contribution of these lymphocyte populations to protective immunity against infectious diseases.

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Tissue Exit: a Novel Control Point in the Accumulation of Antigen-Specific CD8 T Cells in the Influenza A Virus-Infected Lung

Cited by 38 publications

References 58 publications

Effector T Cell Egress via Afferent Lymph Modulates Local Tissue Inflammation

Effector T Cell Egress via Afferent Lymph Modulates Local Tissue Inflammation

Molecular mechanisms of CD8+ T cell trafficking and localization

Guarding the perimeter: protection of the mucosa by tissue-resident memory T cells

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