Collagen Distribution and Expression of Collagen-Binding α1β1 (VLA-1) and α2β1 (VLA-2) Integrins on CD4 and CD8 T Cells during Influenza Infection

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 whereas T cells infiltrating the lung and airways can express both CD49a and CD49b, CD49a expression was most strongly associated with the CD8+ subset. Conversely, though fewer CD4+ T cells expressed CD49a, most CD4+ cells in the lung tissue or airways expressed CD49b. This reciprocal pattern suggested that CD4 and CD8 T cells might localize differently within the lung tissue and this was supported by immunofluorescent analysis. CD8+ cells tended to localize in close proximity to the collagen IV-rich basement membranes of either the airways or blood vessels, whereas CD4+ cells tended to localize in the collagen I-rich interstitial spaces, with few in the airways. These observations suggest that CD4 T cell interaction with the tissue microenvironment is distinct from CD8 T cells and support the concept that CD4+ T cells in peripheral tissues are regulated differently than the CD8 subset.

The α1β1 Integrin and TNF Receptor II Protect Airway CD8+ Effector T Cells from Apoptosis during Influenza 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.…”

“…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).…”

“…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.…”

Tissue-resident natural killer cells in the livers

“…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.…”

“…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).…”