Intrathymic T-cell migration: a combinatorial interplay of extracellular matrix and chemokines?

Cell migration is crucial for intrathymic T-cell differentiation. Chemokines and extracellular matrix proteins per se induce thymocyte migration, and recent data suggest a combinatorial role for these molecules in this event. For example, thymocyte migration induced by fibronectin plus CXCL12/SDF1-alpha (stromal cell-derived factor1-alpha) is higher than that elicited by the chemokine alone. If such interactions are relevant in the thymus, abnormal expression of any of these ligands and/or their corresponding receptors will lead to defects in thymocyte migration. At least in the murine model of Chagas disease, this seems to be the case. Therefore a better knowledge of this complex biological circuitry will provide new clues for understanding thymus physiology and designing therapeutic strategies targeting developing T cells.

[1]  P. Argibay,et al.  Thymocyte depletion in Trypanosoma cruzi infection is mediated by trans-sialidase-induced apoptosis on nurse cells complex , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[2]  W. Savino,et al.  Upregulated expression of fibronectin receptors underlines the adhesive capability of thymocytes to thymic epithelial cells during the early stages of differentiation: lessons from sublethally irradiated mice. , 1999, Blood.

[3]  Thomas Boehm,et al.  Chemokines define distinct microenvironments in the developing thymus , 2000, European journal of immunology.

[4]  J. Cyster,et al.  Balanced responsiveness to chemoattractants from adjacent zones determines B-cell position , 2002, Nature.

[5]  F. Aoudjit,et al.  Gelatinase B (MMP‐9), but not its inhibitor (TIMP‐1), dictates the growth rate of experimental thymic lymphoma , 1999, International journal of cancer.

[6]  R. Schwartz,et al.  Epithelial Cell-Specific Laminin 5 Is Required for Survival of Early Thymocytes1 , 2000, The Journal of Immunology.

[7]  Haichun Xie,et al.  Integrin Functions Play a Key Role in the Differentiation of Thymocytes In Vivo1 , 2001, The Journal of Immunology.

[8]  H. Broxmeyer,et al.  TECK, an efficacious chemoattractant for human thymocytes, uses GPR-9-6/CCR9 as a specific receptor. , 1999, Blood.

[9]  M. Nussenzweig,et al.  Mice lacking the CCR9 CC-chemokine receptor show a mild impairment of early T- and B-cell development and a reduction in T-cell receptor γδ+ gut intraepithelial lymphocytes , 2001 .

[10]  R. Brentani,et al.  Galectin‐3 modulates carbohydrate‐dependent thymocyte interactions with the thymic microenvironment , 2002, European journal of immunology.

[11]  K. Kondo,et al.  Activation of matrix metalloproteinase‐2 is correlated with invasiveness in thymic epithelial tumors , 2001, Journal of surgical oncology.

[12]  W. Savino,et al.  Functional Insulin-Like Growth Factor-1/Insulin-Like Growth Factor-1 Receptor-Mediated Circuit in Human and Murine Thymic Epithelial Cells , 2002, Neuroendocrinology.

[13]  Sharon Engel,et al.  A transmembrane CXC chemokine is a ligand for HIV-coreceptor Bonzo , 2000, Nature Immunology.

[14]  Sergio Romagnani,et al.  Macrophage-Derived Chemokine and EBI1-Ligand Chemokine Attract Human Thymocytes in Different Stage of Development and Are Produced by Distinct Subsets of Medullary Epithelial Cells: Possible Implications for Negative Selection1 , 2000, The Journal of Immunology.

[15]  J. Groopman,et al.  Janus kinase 2 is involved in stromal cell-derived factor-1alpha-induced tyrosine phosphorylation of focal adhesion proteins and migration of hematopoietic progenitor cells. , 2001, Blood.

[16]  H. Broxmeyer,et al.  Differential Chemotactic Behavior of Developing T Cells in Response to Thymic Chemokines , 1998 .

[17]  C. Martínez-A,et al.  Expression of CCR9 beta-chemokine receptor is modulated in thymocyte differentiation and is selectively maintained in CD8(+) T cells from secondary lymphoid organs. , 2001, Blood.

[18]  Philip E. Dawson,et al.  Presentation of chemokine SDF-1α by fibronectin mediates directed migration of T cells , 2000 .

[19]  Yolande Chvatchko,et al.  A Key Role for Cc Chemokine Receptor 4 in Lipopolysaccharide-Induced Endotoxic Shock , 2000, The Journal of experimental medicine.

[20]  M. Hontebeyrie-Joskowicz,et al.  Studies on the thymus in chagas' disease , 1989 .

[21]  J. Bach,et al.  Characterization of the Extracellular Matrix—Containing Giant Perivascular Spaces in the NOD Mouse Thymus , 1993, Diabetes.

[22]  W. Savino,et al.  Neuroendocrine control of thymus physiology. , 2000, Endocrine reviews.

[23]  Eva Jiménez,et al.  Stromal cell-derived factor 1/CXCR4 signaling is critical for early human T-cell development. , 2002, Blood.

[24]  Mark Ellisman,et al.  Cell adhesion and migration are regulated at distinct stages of thymic T cell development: the roles of fibronectin, VLA4, and VLA5 , 1996, The Journal of experimental medicine.

[25]  G. Suzuki,et al.  Pertussis toxin-sensitive signal controls the trafficking of thymocytes across the corticomedullary junction in the thymus. , 1999, Journal of immunology.

[26]  R. Gazzinelli,et al.  Prevalence of CD8+αβ T cells in Trypanosoma cruzi-elicited myocarditis is associated with acquisition of CD62LLowLFA-1HighVLA-4High activation phenotype and expression of IFN-γ-inducible adhesion and chemoattractant molecules , 2001 .

[27]  G. Anderson,et al.  Fibroblast dependency during early thymocyte development maps to the CD25+ CD44+ stage and involves interactions with fibroblast matrix molecules , 1997, European journal of immunology.

[28]  K. Iwabuchi,et al.  Enhancement of stromal cell‐derived factor‐1α‐induced chemotaxis for CD4/8 double‐positive thymocytes by fibronectin and laminin in mice , 2001, Immunology.

[29]  W. Savino,et al.  Phenotypic and Functional Alterations of Thymic Nurse Cells Following AcuteTrypanosoma cruziInfection , 1997 .

[30]  C. Overall,et al.  Matrix Metalloproteinase Activity Inactivates the CXC Chemokine Stromal Cell-derived Factor-1* , 2001, The Journal of Biological Chemistry.

[31]  R. Alon,et al.  The chemokine SDF-1 activates the integrins LFA-1, VLA-4, and VLA-5 on immature human CD34(+) cells: role in transendothelial/stromal migration and engraftment of NOD/SCID mice. , 2000, Blood.

[32]  Inge Nelissen,et al.  Gelatinase B functions as regulator and effector in leukocyte biology , 2001, Journal of leukocyte biology.

[33]  T. Springer,et al.  The chemokine receptor CXCR4 is required for the retention of B lineage and granulocytic precursors within the bone marrow microenvironment. , 1999, Immunity.

[34]  A. Hidalgo,et al.  Chemokine stromal cell-derived factor-1alpha modulates VLA-4 integrin-mediated multiple myeloma cell adhesion to CS-1/fibronectin and VCAM-1. , 2001, Blood.

[35]  Osamu Yoshie,et al.  Role for CCR7 ligands in the emigration of newly generated T lymphocytes from the neonatal thymus. , 2002, Immunity.

[36]  R. Chammas,et al.  The thymic nurse cell complex: an in vitro model for extracellular matrix-mediated intrathymic T cell migration. , 1995, Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas.

[37]  R. Gazzinelli,et al.  Modulation of chemokine production and inflammatory responses in interferon-gamma- and tumor necrosis factor-R1-deficient mice during Trypanosoma cruzi infection. , 2001, The American journal of pathology.

[38]  M. Hontebeyrie-Joskowicz,et al.  Studies on the Thymus in Chagas' Disease II. Thymocyte Subset Fluctuations in Trypanosoma cruzi‐infected mice: Relationship to Stress , 1991, Scandinavian journal of immunology.

[39]  R. Kiessling,et al.  Laminin-8 (alpha4beta1gamma1) is synthesized by lymphoid cells, promotes lymphocyte migration and costimulates T cell proliferation. , 2001, Journal of cell science.

[40]  Ivo Lieberam,et al.  The murine β‐chemokine TARC is expressed by subsets of dendritic cells and attracts primed CD4+ T cells , 1999 .

[41]  E. Butcher,et al.  Cutting edge: developmental switches in chemokine responses during T cell maturation. , 1999, Journal of immunology.

[42]  G. Anderson,et al.  Thymus organ cultures and T‐cell receptor repertoire development , 2000, Immunology.

[43]  C. Overall,et al.  Inflammation dampened by gelatinase A cleavage of monocyte chemoattractant protein-3. , 2000, Science.

[44]  E. Jenkinson,et al.  An Essential Role for Thymic Mesenchyme in Early T Cell Development , 2000, The Journal of experimental medicine.

[45]  A. Villa,et al.  Thymocyte contact or monoclonal antibody-mediated clustering of 3beta1 or 6beta4 integrins activate interleukin-6 (IL-6) transcription factors (NF-kappaB and NF-IL6) and IL-6 production in human thymic epithelial cells. , 1998, Blood.

[46]  E Lazzeri,et al.  Chemokines and lymphopoiesis in human thymus. , 2001, Trends in immunology.

[47]  E. Jenkinson,et al.  Factors regulating stem cell recruitment to the fetal thymus. , 1999, Journal of immunology.

[48]  J. Coligan,et al.  Aberrant Development of Thymocytes in Mice Lacking Laminin-2 , 2000, Developmental immunology.

[49]  J. Coligan,et al.  Alpha 3 beta 1 and alpha 6 beta 1 integrins mediate laminin/merosin binding and function as costimulatory molecules for human thymocyte proliferation. , 1995, Journal of immunology.

[50]  J. Cyster,et al.  Chemokines in lymphopoiesis and lymphoid organ development. , 2001, Current opinion in immunology.

[51]  C. Martínez-A,et al.  The Transient Expression of C-C Chemokine Receptor 8 in Thymus Identifies a Thymocyte Subset Committed to Become CD4+ Single-Positive T Cells1 , 2001, The Journal of Immunology.

[52]  W. Savino,et al.  Role of Extracellular Matrix-Mediated Interactions in Thymocyte Migration , 2000, Developmental immunology.

[53]  I. Weissman,et al.  B Lymphopoiesis in the Thymus1 , 2000, The Journal of Immunology.

[54]  V. Quaranta,et al.  Laminin 5 in the Human Thymus: Control of T Cell Proliferation via α6β4 Integrins , 1999, The Journal of cell biology.

[55]  E. Wolf,et al.  CCR7 Coordinates the Primary Immune Response by Establishing Functional Microenvironments in Secondary Lymphoid Organs , 1999, Cell.

[56]  J. Farber,et al.  Characterization of CCR9 Expression and CCL25/Thymus-Expressed Chemokine Responsiveness During T Cell Development: CD3highCD69+ Thymocytes and γδTCR+ Thymocytes Preferentially Respond to CCL251 , 2002, The Journal of Immunology.

[57]  C. Voermans,et al.  Increased migration of cord blood-derived CD34+ cells, as compared to bone marrow and mobilized peripheral blood CD34+ cells across uncoated or fibronectin-coated filters. , 1999, Experimental hematology.

[58]  K. Kelly,et al.  Analysis of recent thymic emigrants with subset- and maturity-related markers. , 1990, International Immunology.

[59]  E Lazzeri,et al.  Interferon-inducible protein 10, monokine induced by interferon gamma, and interferon-inducible T-cell alpha chemoattractant are produced by thymic epithelial cells and attract T-cell receptor (TCR) alphabeta+ CD8+ single-positive T cells, TCRgammadelta+ T cells, and natural killer-type cells in hum , 2001, Blood.