期刊论文详细信息
Immunity & Ageing
Bone marrow T cells from the femur are similar to iliac crest derived cells in old age and represent a useful tool for studying the aged immune system
Beatrix Grubeck-Loebenstein3  Martin Krismer1  Birgit Weinberger3  Robert Gassner4  Julian Lair1  Rauend Rauf1  Dietmar Herndler-Brandstetter2  Katja Landgraf-Rauf3  Theresa Pritz3 
[1] Department of Orthopedic Surgery, Innsbruck Medical University, Anichstrasse 35, Innsbruck, Austria;Present address: Yale University School of Medicine, 333 Cedar Street, New Haven, CT, USA;Institute for Biomedical Aging Research, University Innsbruck, Rennweg 10, Innsbruck, Austria;Department of Cranio-Maxillofacial and Oral Surgery, Innsbruck Medical University, Anichstrasse 35, Innsbruck, Austria
关键词: Cytomegalovirus;    T cell lines;    Cytokines;    T cells;    Mononuclear cells;    Peripheral blood;    Femur;    Iliac crest;    Bone marrow;   
Others  :  815034
DOI  :  10.1186/1742-4933-10-17
 received in 2012-12-21, accepted in 2013-03-25,  发布年份 2013
PDF
【 摘 要 】

Background

CD4+ and CD8+ T cells reside in the human bone marrow (BM) and show a heightened activation state. However, only small sample sizes are available from sources such as the iliac crest. Larger samples can be obtained from the femur in the course of hip replacement surgery. It was therefore the goal of the present study to compare the phenotype and function of BM T cells from different sources from elderly persons and to investigate how femur derived bone marrow T cells can serve as a tool to gain a better understanding of the role of adaptive immune cells in the BM in old age.

Results

Bone marrow mononuclear cells (BMMC) were isolated from either the iliac crest or the femur shaft. As expected the yield of mononuclear cells was higher from femur than from iliac crest samples. There were no phenotypic differences between BMMC from the two sources. Compared to PBMC, both BM sample types contained fewer naïve and more antigen experienced CD4+ as well as CD8+ T cells, which, in contrast to peripheral cells, expressed CD69. Cytokine production was also similar in T cells from both BM types. Larger sample sizes allowed the generation of T cell lines from femur derived bone marrow using non-specific as well as specific stimulation. The phenotype of T cell lines generated by stimulation with OKT-3 and IL-2 for two weeks was very similar to the one of ex vivo BM derived T cells. Such lines can be used for studies on the interaction of different types of BM cells as shown by co-culture experiments with BM derived stromal cells. Using CMVNLV specific T cell lines we additionally demonstrated that BM samples from the femur are suitable for the generation of antigen specific T cell lines, which can be used in studies on the clonal composition of antigen specific BM T cells.

Conclusion

In conclusion, our results demonstrate that BMMC from the femur shaft are a useful tool for studies on the role of T cells in the BM in old age.

【 授权许可】

   
2013 Pritz et al.; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20140710053235770.pdf 998KB PDF download
Figure 4. 73KB Image download
Figure 3. 40KB Image download
Figure 2. 109KB Image download
Figure 1. 50KB Image download
【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

【 参考文献 】
  • [1]Di Rosa F, Pabst R: The bone marrow: a nest for migratory memory T cells. Trends Immunol 2005, 26:360-366.
  • [2]Tokoyoda K, Zehentmeier S, Chang HD, Radbruch A: Organization and maintenance of immunological memory by stroma niches. Eur J Immunol 2009, 39:2095-2099.
  • [3]Herndler-Brandstetter D, Landgraf K, Jenewein B, Tzankov A, Brunauer R, Brunner S, Parson W, Kloss F, Gassner R, Lepperdinger G, Grubeck-Loebenstein B: Human bone marrow hosts polyfunctional memory CD4+ and CD8+ T cells with close contact to IL-15-producing cells. J Immunol 2011, 186:6965-6971.
  • [4]Herndler-Brandstetter D, Landgraf K, Tzankov A, Jenewein B, Brunauer R, Laschober GT, Parson W, Kloss F, Gassner R, Lepperdinger G, Grubeck-Loebenstein B: The impact of aging on memory T cell phenotype and function in the human bone marrow. J Leukoc Biol 2012, 91:197-205.
  • [5]Abrahamsen JF, Lund-Johansen F, Laerum OD, Schem BC, Sletvold O, Smaaland R: Flow cytometric assessment of peripheral blood contamination and proliferative activity of human bone marrow cell populations. Cytometry 1995, 19:77-85.
  • [6]Shen Y, Wang W, Li X, Liu Z, Markel DC, Ren W: Impacts of age and gender on bone marrow profiles of BMP7, BMPRs and Stro-1(+) cells in patients with total hip replacement. Int Orthop 2012, 36:879-886.
  • [7]Fehrer C, Brunauer R, Laschober G, Unterluggauer H, Reitinger S, Kloss F, Gully C, Gassner R, Lepperdinger G: Reduced oxygen tension attenuates differentiation capacity of human mesenchymal stem cells and prolongs their lifespan. Aging Cell 2007, 6:745-757.
  • [8]Landgraf K, Brunauer R, Lepperdinger G, Grubeck-Loebenstein B: The suppressive effect of mesenchymal stromal cells on T cell proliferation is conserved in old age. Transpl Immunol 2011, 25:167-172.
  • [9]Schwanninger A, Weinberger B, Weiskopf D, Herndler-Brandstetter D, Reitinger S, Gassner C, Schennach H, Parson W, Wurzner R, Grubeck-Loebenstein B: Age-related appearance of a CMV-specific high-avidity CD8+ T cell clonotype which does not occur in young adults. Immun Ageing 2008, 5:14. BioMed Central Full Text
  • [10]Weinberger B, Welzl K, Herndler-Brandstetter D, Parson W, Grubeck-Loebenstein B: CD28(-)CD8(+) T cells do not contain unique clonotypes and are therefore dispensable. Immunol Lett 2009, 127:27-32.
  • [11]Brunner S, Herndler-Brandstetter D, Arnold CR, Wiegers GJ, Villunger A, Hackl M, Grillari J, Moreno-Villanueva M, Burkle A, Grubeck-Loebenstein B: Upregulation of miR-24 is associated with a decreased DNA damage response upon etoposide treatment in highly differentiated CD8(+) T cells sensitizing them to apoptotic cell death. Aging Cell 2012, 11:579-587.
  • [12]Li G, Yu M, Lee WW, Tsang M, Krishnan E, Weyand CM, Goronzy JJ: Decline in miR-181a expression with age impairs T cell receptor sensitivity by increasing DUSP6 activity. Nat Med 2012, 18:1518-1524.
  • [13]Johnson PL, Yates AJ, Goronzy JJ, Antia R: Peripheral selection rather than thymic involution explains sudden contraction in naive CD4 T-cell diversity with age. Proc Natl Acad Sci U S Ain press
  • [14]Tokoyoda K, Zehentmeier S, Hegazy AN, Albrecht I, Grun JR, Lohning M, Radbruch A: Professional memory CD4+ T lymphocytes preferentially reside and rest in the bone marrow. Immunity 2009, 30:721-30.
  • [15]Tokoyoda K, Hauser AE, Nakayama T, Radbruch A: Organization of immunological memory by bone marrow stroma. Nat Rev Immunol 2010, 10:193-200.
  • [16]Abumaree M, Al Jumah M, Pace RA, Kalionis B: Immunosuppressive properties of mesenchymal stem cells. Stem Cell Rev 2011, 8:375-92.
  • [17]Tolar J, Villeneuve P, Keating A: Mesenchymal stromal cells for graft-versus-host disease. Hum Gene Ther 2011, 22:257-62.
  • [18]Le Blanc K, Rasmusson I, Sundberg B, Gotherstrom C, Hassan M, Uzunel M, Ringden O: Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet 2004, 363:1439-41.
  • [19]Peggs K, Verfuerth S, Pizzey A, Ainsworth J, Moss P, Mackinnon S: Characterization of human cytomegalovirus peptide-specific CD8(+) T-cell repertoire diversity following in vitro restimulation by antigen-pulsed dendritic cells. Blood 2002, 99:213-23.
  • [20]Saurwein-Teissl M, Lung TL, Marx F, Gschosser C, Asch E, Blasko I, Parson W, Bock G, Schonitzer D, Trannoy E, Grubeck-Loebenstein B: Lack of antibody production following immunization in old age: association with CD8(+)CD28(-) T cell clonal expansions and an imbalance in the production of Th1 and Th2 cytokines. J Immunol 2002, 168:5893-9.
  • [21]Letsch A, Knoedler M, Na IK, Kern F, Asemissen AM, Keilholz U, Loesch M, Thiel E, Volk HD, Scheibenbogen C: CMV-specific central memory T cells reside in bone marrow. Eur J Immunol 2007, 37:3063-8.
  • [22]Almanzar G, Schwaiger S, Jenewein B, Keller M, Herndler-Brandstetter D, Wurzner R, Schonitzer D, Grubeck-Loebenstein B: Long-term cytomegalovirus infection leads to significant changes in the composition of the CD8+ T-cell repertoire, which may be the basis for an imbalance in the cytokine production profile in elderly persons. J Virol 2005, 79:3675-83.
  • [23]Pawelec G, Akbar A, Caruso C, Effros R, Grubeck-Loebenstein B, Wikby A: Is immunosenescence infectious? Trends Immunol 2004, 25:406-10.
  • [24]Pawelec G, Akbar A, Beverley P, Caruso C, Derhovanessian E, Fulop T, Griffiths P, Grubeck-Loebenstein B, Hamprecht K, Jahn G, Kern F, Koch SD, Larbi A, Maier AB, Macallan D, Moss P, Samson S, Strindhall J, Trannoy E, Wills M: Immunosenescence and Cytomegalovirus: where do we stand after a decade? Immun Ageing 2010, 7:13. BioMed Central Full Text
  • [25]Herndler-Brandstetter D, Schwaiger S, Veel E, Fehrer C, Cioca DP, Almanzar G, Keller M, Pfister G, Parson W, Wurzner R, Schonitzer D, Henson SM, Aspinall R, Lepperdinger G, Grubeck-Loebenstein B: CD25-expressing CD8+ T cells are potent memory cells in old age. J Immunol 2005, 175:1566-74.
  文献评价指标  
  下载次数:29次 浏览次数:36次