Differential survival of leukocyte subsets mediated by synovial, bone marrow, and skin fibroblasts: Site-specific versus activation-dependent survival of T cells and neutrophils
Andrew Filer
MRC Centre for Immune Regulation, University of Birmingham, Birmingham, UK
Search for more papers by this authorGreg Parsonage
MRC Centre for Immune Regulation, University of Birmingham, Birmingham, UK
Search for more papers by this authorEmily Smith
MRC Centre for Immune Regulation, University of Birmingham, Birmingham, UK
Search for more papers by this authorChloe Osborne
MRC Centre for Immune Regulation, University of Birmingham, Birmingham, UK
Search for more papers by this authorS. John Curnow
MRC Centre for Immune Regulation, University of Birmingham, Birmingham, UK
Search for more papers by this authorG. Ed Rainger
MRC Centre for Immune Regulation, University of Birmingham, Birmingham, UK
Search for more papers by this authorKarim Raza
MRC Centre for Immune Regulation, University of Birmingham, Birmingham, UK
Drs. Buckley, Raza, and Salmon have received honoraria and grants (more than $10,000) from Wyeth.
Search for more papers by this authorGerard B. Nash
MRC Centre for Immune Regulation, University of Birmingham, Birmingham, UK
Search for more papers by this authorJanet Lord
MRC Centre for Immune Regulation, University of Birmingham, Birmingham, UK
Search for more papers by this authorMike Salmon
MRC Centre for Immune Regulation, University of Birmingham, Birmingham, UK
Drs. Buckley, Raza, and Salmon have received honoraria and grants (more than $10,000) from Wyeth.
Search for more papers by this authorCorresponding Author
Christopher D. Buckley
MRC Centre for Immune Regulation, University of Birmingham, Birmingham, UK
Drs. Buckley, Raza, and Salmon have received honoraria and grants (more than $10,000) from Wyeth.
Division of Immunity and Infection, Institute for Biomedical Research, University of Birmingham, Edgbaston, Birmingham B15 2TT, UKSearch for more papers by this authorAndrew Filer
MRC Centre for Immune Regulation, University of Birmingham, Birmingham, UK
Search for more papers by this authorGreg Parsonage
MRC Centre for Immune Regulation, University of Birmingham, Birmingham, UK
Search for more papers by this authorEmily Smith
MRC Centre for Immune Regulation, University of Birmingham, Birmingham, UK
Search for more papers by this authorChloe Osborne
MRC Centre for Immune Regulation, University of Birmingham, Birmingham, UK
Search for more papers by this authorS. John Curnow
MRC Centre for Immune Regulation, University of Birmingham, Birmingham, UK
Search for more papers by this authorG. Ed Rainger
MRC Centre for Immune Regulation, University of Birmingham, Birmingham, UK
Search for more papers by this authorKarim Raza
MRC Centre for Immune Regulation, University of Birmingham, Birmingham, UK
Drs. Buckley, Raza, and Salmon have received honoraria and grants (more than $10,000) from Wyeth.
Search for more papers by this authorGerard B. Nash
MRC Centre for Immune Regulation, University of Birmingham, Birmingham, UK
Search for more papers by this authorJanet Lord
MRC Centre for Immune Regulation, University of Birmingham, Birmingham, UK
Search for more papers by this authorMike Salmon
MRC Centre for Immune Regulation, University of Birmingham, Birmingham, UK
Drs. Buckley, Raza, and Salmon have received honoraria and grants (more than $10,000) from Wyeth.
Search for more papers by this authorCorresponding Author
Christopher D. Buckley
MRC Centre for Immune Regulation, University of Birmingham, Birmingham, UK
Drs. Buckley, Raza, and Salmon have received honoraria and grants (more than $10,000) from Wyeth.
Division of Immunity and Infection, Institute for Biomedical Research, University of Birmingham, Edgbaston, Birmingham B15 2TT, UKSearch for more papers by this authorAbstract
Objective
Synovial fibroblasts share a number of phenotype markers with fibroblasts derived from bone marrow. In this study we investigated the role of matched fibroblasts obtained from 3 different sources (bone marrow, synovium, and skin) to test the hypothesis that synovial fibroblasts share similarities with bone marrow–derived fibroblasts in terms of their ability to support survival of T cells and neutrophils.
Methods
Matched synovial, bone marrow, and skin fibroblasts were established from 8 different patients with rheumatoid arthritis who were undergoing knee or hip surgery. Resting or activated fibroblasts were cocultured with either CD4 T cells or neutrophils, and the degree of leukocyte survival, apoptosis, and proliferation were measured.
Results
Fibroblasts derived from all 3 sites supported increased survival of CD4 T cells, mediated principally by interferon-β. However, synovial and bone marrow fibroblasts shared an enhanced site-specific ability to maintain CD4 T cell survival in the absence of proliferation, an effect that was independent of fibroblast activation or proliferation but required direct T cell–fibroblast cell contact. In contrast, fibroblast-mediated neutrophil survival was less efficient, being independent of the site of origin of the fibroblast but dependent on prior fibroblast activation, and mediated solely by soluble factors, principally granulocyte–macrophage colony-stimulating factor.
Conclusion
These results suggest an important functional role for fibroblasts in the differential accumulation of leukocyte subsets in a variety of tissue microenvironments. The findings also provide a potential explanation for site-specific differences in the pattern of T cell and neutrophil accumulation observed in chronic inflammatory diseases.
REFERENCES
- 1 McInnes IB, Leung BP, Liew FY. Cell-cell interactions in synovitis: interactions between T lymphocytes and synovial cells. Arthritis Res 2000; 2: 374–8.
- 2 Postlethwaite AE. Role of T cells and cytokines in effecting fibrosis. Int Rev Immunol 1995; 12: 247–58.
- 3 Rezzonico R, Burger D, Dayer JM. Direct contact between T lymphocytes and human dermal fibroblasts or synoviocytes down-regulates types I and III collagen production via cell-associated cytokines. J Biol Chem 1998; 273: 18720–8.
- 4 Yamamura Y, Gupta R, Morita Y, He X, Pai R, Endres J, et al. Effector function of resting T cells: activation of synovial fibroblasts. J Immunol 2001; 166: 2270–5.
- 5 Miranda-Carus ME, Balsa A, Benito-Miguel M, Perez DA, Martin-Mola E. IL-15 and the initiation of cell contact-dependent synovial fibroblast-T lymphocyte cross-talk in rheumatoid arthritis: effect of methotrexate. J Immunol 2004; 173: 1463–76.
- 6 Scott S, Pandolfi F, Kurnick JT. Fibroblasts mediate T cell survival: a proposed mechanism for retention of primed T cells. J Exp Med 1990; 172: 1873–6.
- 7 Salmon M, Scheel-Toellner D, Huissoon AP, Pilling D, Shamsadeen N, Hyde H, et al. Inhibition of T cell apoptosis in the rheumatoid synovium. J Clin Invest 1997; 99: 439–46.
- 8
Pilling D,
Akbar AN,
Girdlestone J,
Orteu CH,
Borthwick NJ,
Amft N, et al.
Interferon-β mediates stromal cell rescue of T cells from apoptosis.
Eur J Immunol
1999;
29:
1041–50.
10.1002/(SICI)1521-4141(199903)29:03<1041::AID-IMMU1041>3.0.CO;2-# CAS PubMed Web of Science® Google Scholar
- 9 Hayashida K, Shimaoka Y, Ochi T, Lipsky PE. Rheumatoid arthritis synovial stromal cells inhibit apoptosis and up-regulate Bcl-xL expression by B cells in a CD49/CD29-CD106-dependent mechanism. J Immunol 2000; 164: 1110–6.
- 10 Burger JA, Zvaifler NJ, Tsukada N, Firestein GS, Kipps TJ. Fibroblast-like synoviocytes support B-cell pseudoemperipolesis via a stromal cell-derived factor-1- and CD106 (VCAM-1)-dependent mechanism. J Clin Invest 2001; 107: 305–15.
- 11 Ohata J, Zvaifler NJ, Nishio M, Boyle DL, Kalled SL, Carson DA, et al. Fibroblast-like synoviocytes of mesenchymal origin express functional B cell-activating factor of the TNF family in response to proinflammatory cytokines. J Immunol 2005; 174: 864–70.
- 12 Edwards SW, Hallett MB. Seeing the wood for the trees: the forgotten role of neutrophils in rheumatoid arthritis. Immunol Today 1997; 18: 320–4.
- 13 Daffern PJ, Jagels MA, Hugli TE. Multiple epithelial cell-derived factors enhance neutrophil survival: regulation by glucocorticoids and tumor necrosis factor-α. Am J Respir Cell Mol Biol 1999; 21: 259–67.
- 14 Laan M, Prause O, Miyamoto M, Sjostrand M, Hytonen AM, Kaneko T, et al. A role of GM-CSF in the accumulation of neutrophils in the airways caused by IL-17 and TNF-α. Eur Respir J 2003; 21: 387–93.
- 15 Stanford SJ, Pepper JR, Burke-Gaffney A, Mitchell JA. Cytokine-activated human vascular smooth muscle delays apoptosis of neutrophils: relevance of interactions between cyclo-oxygenase-2 and colony-stimulating factors. FASEB J 2001; 15: 1813–5.
- 16 Chang HY, Chi JT, Dudoit S, Bondre C, van de RM, Botstein D, et al. Diversity, topographic differentiation, and positional memory in human fibroblasts. Proc Natl Acad Sci U S A 2002; 99: 12877–82.
- 17 Merville P, Dechanet J, Desmouliere A, Durand I, de Bouteiller O, Garrone P, et al. Bcl-2+ tonsillar plasma cells are rescued from apoptosis by bone marrow fibroblasts. J Exp Med 1996; 183: 227–36.
- 18 Sellge G, Lorentz A, Gebhardt T, Levi-Schaffer F, Bektas H, Manns MP, et al. Human intestinal fibroblasts prevent apoptosis in human intestinal mast cells by a mechanism independent of stem cell factor, IL-3, IL-4, and nerve growth factor. J Immunol 2004; 172: 260–7.
- 19 Marinova-Mutafchieva L, Taylor P, Funa K, Maini RN, Zvaifler NJ. Mesenchymal cells expressing bone morphogenetic protein receptors are present in the rheumatoid arthritis joint. Arthritis Rheum 2000; 43: 2046–55.
- 20 De Bari C, Dell'Accio F, Tylzanowski P, Luyten FP. Multipotent mesenchymal stem cells from adult human synovial membrane. Arthritis Rheum 2001; 44: 1928–42.
- 21 Edwards JC. Fibroblast biology: development and differentiation of synovial fibroblasts in arthritis. Arthritis Res 2000; 2: 344–7.
- 22 Jorgensen C, Noel D, Gross G. Could inflammatory arthritis be triggered by progenitor cells in the joints? Ann Rheum Dis 2002; 61: 6–9.
- 23 Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988; 31: 315–24.
- 24 Scaife S, Brown R, Kellie S, Filer A, Martin S, Thomas AM, et al. Detection of differentially expressed genes in synovial fibroblasts by restriction fragment differential display. Rheumatology (Oxford) 2004; 43: 1346–52.
- 25 Parsonage G, Falciani F, Burman A, Filer A, Ross E, Bofill M, et al. Global gene expression profiles in fibroblasts from synovial, skin and lymphoid tissue reveals distinct cytokine and chemokine expression patterns. Thromb Haemost 2003; 90: 688–97.
- 26 Bradfield PF, Amft N, Vernon-Wilson E, Exley AE, Parsonage G, Rainger GE, et al. Rheumatoid fibroblast-like synoviocytes overexpress the chemokine stromal cell–derived factor 1 (CXCL12), which supports distinct patterns and rates of CD4+ and CD8+ T cell migration within synovial tissue. Arthritis Rheum 2003; 48: 2472–82.
- 27 Wang K, Scheel-Toellner D, Wong SH, Craddock R, Caamano J, Akbar AN, et al. Inhibition of neutrophil apoptosis by type 1 IFN depends on cross-talk between phosphoinositol 3-kinase, protein kinase C-δ, and NF-κB signaling pathways. J Immunol 2003; 171: 1035–41.
- 28 Bucala R, Ritchlin C, Winchester R, Cerami A. Constitutive production of inflammatory and mitogenic cytokines by rheumatoid synovial fibroblasts. J Exp Med 1991; 173: 569–74.
- 29 Firestein GS. Invasive fibroblast-like synoviocytes in rheumatoid arthritis: passive responders or transformed aggressors? Arthritis Rheum 1996; 39: 1781–90.
- 30 Shimaoka Y, Attrep JF, Hirano T, Ishihara K, Suzuki R, Toyosaki T, et al. Nurse-like cells from bone marrow and synovium of patients with rheumatoid arthritis promote survival and enhance function of human B cells. J Clin Invest 1998; 102: 606–18.
- 31 Salmon M, Pilling D, Borthwick NJ, Viner N, Janossy G, Bacon PA, et al. The progressive differentiation of primed T cells is associated with an increasing susceptibility to apoptosis. Eur J Immunol 1994; 24: 892–9.
- 32 Gombert W, Borthwick NJ, Wallace DL, Hyde H, Bofill M, Pilling D, et al. Fibroblasts prevent apoptosis of IL-2-deprived T cells without inducing proliferation: a selective effect on Bcl-XL expression. Immunology 1996; 89: 397–404.
- 33 Bombara MP, Webb DL, Conrad P, Marlor CW, Sarr T, Ranges GE, et al. Cell contact between T cells and synovial fibroblasts causes induction of adhesion molecules and cytokines. J Leukoc Biol 1993; 54: 399–406.
- 34 Buckley CD, Amft N, Bradfield PF, Pilling D, Ross E, Arenzana-Seisdedos F, et al. Persistent induction of the chemokine receptor CXCR4 by TGF-β1 on synovial T cells contributes to their accumulation within the rheumatoid synovium. J Immunol 2000; 165: 3423–9.
- 35 Suzuki Y, Rahman M, Mitsuya H. Diverse transcriptional response of CD4(+) T cells to stromal cell-derived factor (SDF)-1: cell survival promotion and priming effects of SDF-1 on CD4(+) T cells. J Immunol 2001; 167: 3064–73.
- 36 Cho ML, Yoon CH, Hwang SY, Park MK, Min SY, Lee SH, et al. Effector function of type II collagen–stimulated T cells from rheumatoid arthritis patients: cross-talk between T cells and synovial fibroblasts. Arthritis Rheum 2004; 50: 776–84.
- 37 Marrack P, Kappler J, Mitchell T. Type I interferons keep activated T cells alive. J Exp Med 1999; 189: 521–30.
- 38 Southey AK, O'Connor CM, Fitzgerald MX. The effect of fibroblast conditioned medium on neutrophil survival and activation. Biochem Soc Trans 1994; 22: 52S.
- 39 Ling CJ, Owen WF Jr, Austen KF. Human fibroblasts maintain the viability and augment the functional response of human neutrophils in culture. J Clin Invest 1990; 85: 601–4.
- 40 Walmsley SR, Print C, Farahi N, Peyssonnaux C, Johnson RS, Cramer T, et al. Hypoxia-induced neutrophil survival is mediated by HIF-1α-dependent NF-κB activity. J Exp Med 2005; 201: 105–15.
- 41 Morales-Ducret J, Wayner E, Elices MJ, Alvaro-Gracia JM, Zvaifler NJ, Firestein GS. α4/β1 integrin (VLA-4) ligands in arthritis: vascular cell adhesion molecule-1 expression in synovium and on fibroblast-like synoviocytes. J Immunol 1992; 149: 1424–31.
- 42 Rodriguez MC, Bernad A, Aracil M. Interleukin-6 deficiency affects bone marrow stromal precursors, resulting in defective hematopoietic support. Blood 2004; 103: 3349–54.
- 43 Vallejo AN, Yang H, Klimiuk PA, Weyand CM, Goronzy JJ. Synoviocyte-mediated expansion of inflammatory T cells in rheumatoid synovitis is dependent on CD47-thrombospondin 1 interaction. J Immunol 2003; 171: 1732–40.
- 44 Corrigall VM, Solau-Gervais E, Panayi GS. Lack of CD80 expression by fibroblast-like synoviocytes leading to anergy in T lymphocytes. Arthritis Rheum 2000; 43: 1606–15.
- 45 Numasaki M, Lotze MT, Sasaki H. Interleukin-17 augments tumor necrosis factor-α-induced elaboration of proangiogenic factors from fibroblasts. Immunol Lett 2004; 93: 39–43.
- 46 Min DJ, Cho ML, Lee SH, Min SY, Kim WU, Min JK, et al. Augmented production of chemokines by the interaction of type II collagen–reactive T cells with rheumatoid synovial fibroblasts. Arthritis Rheum 2004; 50: 1146–55.
- 47 Burger D. Cell contact interactions in rheumatology. Arthritis Res 2000; 2: 472–6.
- 48 Winter SS, Sweatman JJ, Lawrence MB, Rhoades TH, Hart AL, Larson RS. Enhanced T-lineage acute lymphoblastic leukaemia cell survival on bone marrow stroma requires involvement of LFA-1 and ICAM-1. Br J Haematol 2001; 115: 862–71.
- 49 Bell AL, Irvine AE, Magill K, McKane R. Fate of inflammatory neutrophils within the joint. Rheumatology (Oxford) 2003; 41: 1249–60.
