Abstract:Most viral infections occur in extralymphoid tissues, yet the mechanisms that regulate lymphocytes in these environments are poorly understood. One feature common to many extralymphoid environments is an abundance of extracellular matrix. We have studied the expression of two members of the β1 integrin family of collagen-binding receptors, α1β1 and α2β1 (CD49a, VLA-1 and CD49b, VLA-2, respectively), on CD4 and CD8 T cells during the response to influenza infection in the lung. Flow cytometry showed that wherea… Show more
“…The ␣ 1  1 collagen-binding integrin VLA-1 is an important feature of memory CD8 T cells that allows them to be maintained in extralymphoid sites (9) and regulates the precise localization of CD4 and CD8 T cells within the collagen-rich structure of the lung (28). In this present study, we focused on the function of VLA-1 during the acute phase of the infection.…”
Section: Discussionmentioning
confidence: 99%
“…VLA-1 is the major receptor for type IV collagen, which is abundant in the lung and found in the basement membranes of the endothelium and epithelium (28,47). In lymphoid tissues, fibroblastic reticular cells envelop collagen fibrils, and that these collagen fibrils are located in the interfollicular zones (48,49).…”
Section: Discussionmentioning
confidence: 99%
“…Although we have shown that CD8 T cells in the lung are preferentially in close proximity to collagen IV (9,28), their proximity to collagen in the spleen is unknown. Lungs and spleens from acutely infected animals were removed, and frozen sections (5-10 m thick) were stained with fluorescence-labeled rat anti-mouse CD8a and rabbit anti-mouse type IV collagen.…”
Section: Vla-1 ϩ Cd8 T Cells Have Enhanced Access To Type IV Collagenmentioning
Primary viral infections of the lung induce potent effector CD8 T cell responses. To function in the influenza-infected airways, CD8 T cells must be able to resist cell death. The majority of the CD8 T cells in the airways and lung parenchyma expressed CD49a, the α-chain of the type IV collagen receptor VLA-1, and these cells were highly activated, producing both IFN-γ and TNF-α. In the airways, where type IV collagen is abundant, but not the spleen, the CD49a+ CD8 cells had reduced proportions of annexin V and caspase 8, and >80% expressed the TNF-α receptor II, while Fas, TNFR-I, and CD27 expression were similar to CD49a− cells. Furthermore, the CD49a+, but not CD49a−, CD8 T cells from the airways were resistant to active induction of apoptosis in the presence of type IV collagen and TNF-α in vitro. We propose that TNFR-II and the VLA-1 synergize to protect effector CD8 T cells in the infected airways from apoptosis during the acute infection.
“…The ␣ 1  1 collagen-binding integrin VLA-1 is an important feature of memory CD8 T cells that allows them to be maintained in extralymphoid sites (9) and regulates the precise localization of CD4 and CD8 T cells within the collagen-rich structure of the lung (28). In this present study, we focused on the function of VLA-1 during the acute phase of the infection.…”
Section: Discussionmentioning
confidence: 99%
“…VLA-1 is the major receptor for type IV collagen, which is abundant in the lung and found in the basement membranes of the endothelium and epithelium (28,47). In lymphoid tissues, fibroblastic reticular cells envelop collagen fibrils, and that these collagen fibrils are located in the interfollicular zones (48,49).…”
Section: Discussionmentioning
confidence: 99%
“…Although we have shown that CD8 T cells in the lung are preferentially in close proximity to collagen IV (9,28), their proximity to collagen in the spleen is unknown. Lungs and spleens from acutely infected animals were removed, and frozen sections (5-10 m thick) were stained with fluorescence-labeled rat anti-mouse CD8a and rabbit anti-mouse type IV collagen.…”
Section: Vla-1 ϩ Cd8 T Cells Have Enhanced Access To Type IV Collagenmentioning
Primary viral infections of the lung induce potent effector CD8 T cell responses. To function in the influenza-infected airways, CD8 T cells must be able to resist cell death. The majority of the CD8 T cells in the airways and lung parenchyma expressed CD49a, the α-chain of the type IV collagen receptor VLA-1, and these cells were highly activated, producing both IFN-γ and TNF-α. In the airways, where type IV collagen is abundant, but not the spleen, the CD49a+ CD8 cells had reduced proportions of annexin V and caspase 8, and >80% expressed the TNF-α receptor II, while Fas, TNFR-I, and CD27 expression were similar to CD49a− cells. Furthermore, the CD49a+, but not CD49a−, CD8 T cells from the airways were resistant to active induction of apoptosis in the presence of type IV collagen and TNF-α in vitro. We propose that TNFR-II and the VLA-1 synergize to protect effector CD8 T cells in the infected airways from apoptosis during the acute infection.
“…CD49a is also known as integrin α1 and can associate with the integrin β1 subunit (CD29) to form the CD49a/CD29 (VLA-1) heterodimer, which is responsible for retaining lymphocytes in tissues (Ray et al, 2004;Richter et al, 2007). By parabiosis studies, CD49a was also found to be a marker of trNK cells in other tissues.…”
Section: Cd49a As a Common Marker For Trnk Cellsmentioning
confidence: 89%
“…By parabiosis studies, CD49a was also found to be a marker of trNK cells in other tissues. Akin to the liver, uterus, skin and adipose contain high frequency of CD49a + DX5 − trNK cells (Richter et al, 2007;Sojka et al, 2014a). In contrast to liver and skin trNK cells, uterus NK cells are T-bet-independent and express high levels of Eomes (Sojka et al, 2014a;Tayade et al, 2005).…”
Section: Cd49a As a Common Marker For Trnk Cellsmentioning
Nature killer (NK) cells are important lymphocytes of the innate immune system, well known for their pivotal roles in immune surveillance and defense against tumor and virus-infected cells. Current studies have revealed that NK cells are not a homogeneous population, but instead consist of distinct subsets with diverse characteristics. As an organ with predominant innate immunity, the liver is enriched with NK cells, among which two distinct NK cell subsets have recently been identified: conventional NK (cNK) cells and tissue-resident NK (trNK) cells. Liver trNK cells are markedly different from cNK cells in many aspects, representing a new lineage of innate lymphoid cell (ILC) family. Here, we summarize the phenotypic and functional features of liver trNK cells, and review current knowledge regarding developmental pathway of liver trNK cells. We also overview recent advances in human liver trNK cells and discuss the striking shared hallmarks of trNK cells in different tissues.
Complement receptors are membrane proteins, expressed on cells involved in the immune response, which bind a wide range of the protein fragments generated in the course of complement activation. Through these cellular interactions, the complement system plays a crucial role combating infection. Thus, complement is instrumental in the recruitment of blood leucocytes to a site of inflammation, in promoting phagocytosis and/or extracellular killing of the microorganisms by these cells and in clearance of particulate and soluble immune complexes (ICs) generated at the infected site or released in the circulation. Furthermore, complement is intimately involved in the development of an acquired immune response towards invading pathogens both through the induction of primary B‐cell responses and through shaping of T‐cell responses towards the antigen. This article presents a systematic account of the complement receptors in terms of their structure, cellular distribution and biological and signalling functions.
Key concepts:
Structural diversity of receptors reflecting the diversity of the complement fragments engaged.
Functional diversity, depending on the type of complement fragment involved and/or the type of cells expressing the appropriate receptor.
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