Characterization of a conduit system containing laminin-5 in the human thymus: a potential transport system for small molecules (original) (raw)
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Developmentally regulated interactions of human thymocytes with different laminin isoforms
Immunology, 2002
The gene family of heterotrimeric laminin molecules consists of at least 15 naturally occurring isoforms which are formed by five different a, three b and three c subunits. The expression pattern of the individual laminin chains in the human thymus was comprehensively analysed in the present study. Whereas laminin isoforms containing the laminin a1 chain (e.g. LN-1) were not present in the human thymus, laminin isoforms containing the a2 chain (LN-2/4) or the a5 chain (LN-10/11) were expressed in the subcapsular epithelium and in thymic blood vessels. Expression of the laminin a4 chain seemed to be restricted to endothelial cells of the thymus, whereas the LN-5 isoform containing the a3 chain could be detected on medullary thymic epithelial cells and weakly in the subcapsular epithelium. As revealed by cell attachment assays, early CD4 x CD8 x thymocytes which are localized in the thymus beneath the subcapsular epithelium adhered strongly to LN-10/11, but not to LN-1, LN-2/4 or LN-5. Adhesion of these thymocytes to LN-10/11 was mediated by the integrin a6b1. During further development, the cortically localized CD4 + CD8 + thymocytes have lost the capacity to adhere to laminin-10/11. Neither do these cells adhere to any other laminin isoform tested. However, the more differentiated single positive CD8 + thymocytes which were mainly found in the medulla were able to bind to LN-5 which is expressed by medullary epithelial cells. Interactions of CD8 + thymocytes with LN-5 were integrin a6b4-dependent. These results show that interactions of developing human thymocytes with different laminin isoforms are spatially and developmentally regulated.
Extracellular matrix proteins in intrathymic T-cell migration and differentiation?
Immunology Today, 1993
T-cell differentiation is the process by which bone marrow-derived precursors enter the thymus and develop into T cells. They expand, rearrange and express the Tcell receptor (TCR) genes and a number of other surface molecules, and if they survive positive and negative selection, are released into the peripheryL As they differentiate, th]}anocytes migrate within the thymic lobules, from the cortex to the medulla. The molecular basis for such migration process probably involves sequential interactions mediated by membrane receptors and co-receptors expressed by thymocytes and microenvironmental cells. There are two, nonexclusive, models for this process (Fig. 1): either direct cell-cell contact, allowing thymocytes to move onto the cytoplasmic processes of microenvironmental cells, or bridging by ext~acellular matrix (ECM) elements, establishing transient links between thymocyte and m~cr~nvh-onmental--"---~ t:en memorane receptors. Q Fig. 1. Representation of two distinct cell-cell interactions involving differentiating tlrymocytes and tbymic microenvironmental cells. (a) Shows tbymo-~. es establishing interaaions via receptors that directly bind counter-receptors in the microenvirGnmental cell. Alternatively (b) shows the interactions mediated by an ECM molecule.
Extracellular matrix components of the mouse thymic microenvironment
Cellular Immunology, 1991
We studied the effects of recombinant interferon-y (IFN-7) on some aspects of the physiology of two murine thymic epithelial cell (TEC) lines. Besides the expected induction of MHC class II antigens, this lymphokine was able to modulate the extracellular matrix (ECM) expression by growing TEC, as well as modulate their adhesion and proliferation patterns. As regards the influence of rIFN-7 on ECM expression, we observed that when applied in very low doses, it promoted an increase in the amounts of basement membrane proteins, mainly fibronectin. In contrast, relatively high doses of this lymphokine (lOI to lo* IU/ml) induced the opposite effect. Interestingly, both the stimulatory and the blocking effects of IFN-y on ECM expression were paralleled by equivalent modulation of cell proliferation, in both mouse and rat TEC lines. It should be pointed out that all these effects could be significantly abrogated by an anti-IFN-y monoclonal antibody. Searching for a putative mechanism that could be involved in the modulation of TEC proliferation by IFNy, we observed a clear-cut positive correlation between cell adhesion and proliferation of TEC growing onto ECM-containing substrata produced following IFN-7 treatment. The bulk of the data presented herein suggests that IFN-y may play a relevant role in TEC physiology and ontogeny, not only by inducing MHC class II antigen expression but also by regulating TEC growth via the control of extracellular matrix production by these cells.
Intrathymic T-cell migration: a combinatorial interplay of extracellular matrix and chemokines?
Trends in Immunology, 2002
From the entrance of T-cell precursors into the thymus to the exit of mature cells from the organ, a vast body of interactions promotes the complex process of T-cell differentiation, which is already described in textbooks [1], and is not within the scope of this review. What is relevant herein is the fact that thymocyte differentiation occurs as cells migrate within the thymic lobules. As illustrated in , most of the immature thymocytes, including those bearing the phenotypes T-cell receptor (TCR) − CD3 − CD4 − CD8 − and TCR low CD3 low CD4 + CD8 + are located cortically, whereas mature TCR high CD3 high CD4 + CD8 − and TCR high CD3 high CD4 − CD8 + cells (that will normally leave the thymus and traffic to peripheral lymphoid organs) are found in the medulla. also shows that during the course of their journey within the thymus, developing thymocytes encounter cortical and medullary microenvironments, through distinct cell-cell and cell-matrix interactions . Cell migration is thus a crucial event for intrathymic T-cell differentiation. A series of recent data led us to revisit this field and propose that chemokines might act in concert with extracellular matrix (ECM), resulting in the migration of a given cell subset, either within the thymus or at the entrance into and/or exit from the organ. Moreover, as seen in some of the examples discussed here, modulation of cell migration-related molecules might result in changes in thymocyte differentiation.
The Journal of Immunology, 2004
We have previously shown that laminin-5 is expressed in the human thymic medulla, in which mature thymocytes are located. We now report that laminin-5 promotes migration of mature medullary thymocytes, whereas it has no effect on cortical immature thymocytes. Migration was inhibited by blocking mAbs directed against laminin-5 integrin receptors and by inhibitors of metalloproteinases. Interactions of thymocytes with laminin-5 induced a strong up-regulation of active metalloproteinase-14. However, we found that thymocytes did not cleave the laminin-5 ␥ 2 chain, suggesting that they do not use the same pathway as epithelial cells to migrate on laminin-5. Interactions of thymocytes with laminin-5 also induced the release of a soluble fragment of CD44 cell surface molecule. Moreover, CD44-rich supernatants induced thymocyte migration in contrast with supernatants depleted in CD44 by immunoadsorption. CD44 cleavage was recently reported to be due to metalloproteinase-14 activation and led to increased migration in cancer cells. Thus, in this study, we show that laminin-5 promotes human mature thymocyte migration in vitro via a multimolecular mechanism involving laminin-5 integrin receptors, metalloproteinase-14 and CD44. These data suggest that, in vivo, laminin-5 may function in the migration of mature thymocytes within the medulla and be part of the thymic emigration process.
Immunity, 2005
can phagocytose antigens and, subsequently, traffic via 22185 Lund the afferent lymphatics into the T cell area of the draining Sweden lymph node to initiate immune responses (Cavanagh 2 Department of Dermatology and Von Andrian, 2002; Manickasingham and Reis e University of Erlangen Sousa, 2001; Randolph, 2001). This pathway is well char-91052 Erlangen acterized, and there is recent evidence that steady state Germany migration of DC into the lymph node also occurs in 3 Department of Experimental Medicine I the healthy organism, which may serve to continuously University of Erlangen tolerize T cells against self antigens (Lutz and Schuler, 91054 Erlangen 2002; Steinman et al., 2003). A second pathway of anti-Germany gen delivery is less well defined and functions indepen-4 Department of Anatomy and Cell Biology dently of cellular trafficking along the lymphatics. Sev-McGill University eral studies have shown that peripherally applied Montreal H3A 2B2 soluble antigen is taken up, presented, and cross pre-Canada sented by resident DC in the T cell area of the draining 5 Department of Functional and Applied Anatomy lymph node. This happens before there is any detectable Medical School of Hannover immigration of DC from the periphery (Ingulli et al., 2002; 30625 Hannover Itano et al., 2003; Maurer et al., 2002; Pior et al., 1999). Germany
The lymph node stromal laminin α 5 shapes alloimmunity
2020
2 6 0 2 jci.org Volume 130 Number 5 May 2020 Introduction The lymph node (LN) is the central hub that exchanges antigenpresenting cells and immune cells with peripheral tissues or blood, permitting T cells to encounter cognate antigens and orchestrating T lymphocyte immune responses (1, 2). LN architecture is primarily constructed by a group of nonhematopoietic stromal cells, which constitute approximately 1% of LN cellularity and establish specialized niches (3, 4). The LN stromal cell (LNSC) framework directs immune cell trafficking within designated compartments, which dictate leukocyte functions (5, 6). The LN 3-dimensional structure is compartmentalized by LNSCs and identified as (i) the superficial cortex constituted by follicles and interfollicular cortex; (ii) the paracortex constituted by deep cortical units; and (iii) the medulla constituted by medullary cords and medullary sinuses (7). The cortical ridge (CR) in the paracortex is the region where T lymphocytes enter from ...