Journal of Clinical Immunology

, Volume 31, Issue 5, pp 744–751 | Cite as

Defective T Cell Chemotaxis to Sphingosine 1-Phosphate and Chemokine CCL21 in Idiopathic T Lymphocytopenia

  • Edward J. Goetzl
  • Janice B. Schwartz
  • Mei-Chuan Huang


T cell chemotaxis to sphingosine 1-phosphate (S1P) and the chemokines CCL21 and CCL5 was studied in ten adults with T lymphocytopenia, other immunological abnormalities (nine of ten), and frequent bacterial infections (seven of ten). Mean chemotactic responses to S1P of CD4 T cells from CD4 T lymphocytopenic patients and of CD8 T cells from CD8 T lymphocytopenic patients were significantly lower than those of healthy matched controls. Chemotaxis to CCL21 was lower than that of controls for CD4 T cells of three CD4 T lymphocytopenic patients and for CD8 T cells of three CD8 T lymphocytopenic patients, but none of the T cells of patients had diminished chemotaxis to CCL5. Defective T cell chemotactic responses to S1P and some chemokines may lead to subset-selective abnormal T cell trafficking and chronic T cell lymphocytopenia.


Human T lymphocytes chemotaxis lipid mediator chemokines 



Hypoxanthine-guanine phosphoribosyltransferase


Sphingosine 1-phosphate


Idiopathic T lymphocytopenia



This research was supported by a grant from the Kenneth Rainin Foundation. The authors are grateful to Judith H. Goetzl for preparation of figure graphics and textual editing.

Conflict of Interest

The authors declare no conflicts of interest.


  1. 1.
    Zonios DI et al. Idiopathic CD4+ lymphocytopenia: natural history and prognostic factors. Blood. 2008;112(2):287–94.PubMedCrossRefGoogle Scholar
  2. 2.
    Luo L, Li T. Idiopathic CD4 lymphocytopenia and opportunistic infection—an update. FEMS Immunol Med Microbiol. 2008;54(3):283–9.PubMedCrossRefGoogle Scholar
  3. 3.
    Mukherjee A, Lodha R, Kabra SK. Idiopathic CD4+ T-cell lymphocytopenia. Indian J Pediatr. 2009;76(4):430–2.PubMedCrossRefGoogle Scholar
  4. 4.
    Liao JJ et al. Immunosuppressive human anti-lymphocyte autoantibodies specific for the type 1 sphingosine 1-phosphate receptor. Faseb J. 2009;23(6):1786–96.PubMedCrossRefGoogle Scholar
  5. 5.
    Scott-Algara D et al. Idiopathic CD4+ T-cell lymphocytopenia is associated with impaired membrane expression of the chemokine receptor CXCR4. Blood. 2010;115(18):3708–17.PubMedCrossRefGoogle Scholar
  6. 6.
    Mori S et al. Mice lacking expression of the chemokines CCL21-ser and CCL19 (plt mice) demonstrate delayed but enhanced T cell immune responses. J Exp Med. 2001;193(2):207–18.PubMedCrossRefGoogle Scholar
  7. 7.
    Yilmaz-Demirdag Y et al. Interleukin-2 treatment for persistent cryptococcal meningitis in a child with idiopathic CD4(+) T lymphocytopenia. Allergy Asthma Proc. 2008;29(4):421–4.PubMedCrossRefGoogle Scholar
  8. 8.
    Trojan T, Collins R, Khan DA. Safety and efficacy of treatment using interleukin-2 in a patient with idiopathic CD4(+) lymphopenia and Mycobacterium avium-intracellulare. Clin Exp Immunol. 2009;156(3):440–5.PubMedCrossRefGoogle Scholar
  9. 9.
    Rosen H, Goetzl EJ. Sphingosine 1-phosphate and its receptors: an autocrine and paracrine network. Nat Rev Immunol. 2005;5(7):560–70.PubMedCrossRefGoogle Scholar
  10. 10.
    Pappu R et al. Promotion of lymphocyte egress into blood and lymph by distinct sources of sphingosine-1-phosphate. Science. 2007;316(5822):295–8.PubMedCrossRefGoogle Scholar
  11. 11.
    Graeler M, Goetzl EJ. Activation-regulated expression and chemotactic function of sphingosine 1-phosphate receptors in mouse splenic T cells. Faseb J. 2002;16(14):1874–8.PubMedCrossRefGoogle Scholar
  12. 12.
    Matloubian M, Lo CG, Cinamon G, Lesneski MJ, Xu Y, Brinkmann V, et al. Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1. Nature. 2004;427:355–60.PubMedCrossRefGoogle Scholar
  13. 13.
    Goetzl EJ, Rosen H. Regulation of immunity by lysosphingolipids and their G protein-coupled receptors. J Clin Invest. 2004;114(11):1531–7.PubMedGoogle Scholar
  14. 14.
    Graler MH, Goetzl EJ. The immunosuppressant FTY720 down-regulates sphingosine 1-phosphate G-protein-coupled receptors. Faseb J. 2004;18(3):551–3.PubMedGoogle Scholar
  15. 15.
    Huang MC et al. Human CD4–8-T cells are a distinctive immunoregulatory subset. Faseb J. 2010;24(7):2558–66.PubMedCrossRefGoogle Scholar
  16. 16.
    Graler MH et al. Immunological effects of transgenic constitutive expression of the type 1 sphingosine 1-phosphate receptor by mouse lymphocytes. J Immunol. 2005;174(4):1997–2003.PubMedGoogle Scholar
  17. 17.
    Gunn MD et al. Mice lacking expression of secondary lymphoid organ chemokine have defects in lymphocyte homing and dendritic cell localization. J Exp Med. 1999;189(3):451–60.PubMedCrossRefGoogle Scholar
  18. 18.
    Miyasaka M, Tanaka T. Lymphocyte trafficking across high endothelial venules: dogmas and enigmas. Nat Rev Immunol. 2004;4(5):360–70.PubMedCrossRefGoogle Scholar
  19. 19.
    Mueller SN et al. Regulation of homeostatic chemokine expression and cell trafficking during immune responses. Science. 2007;317(5838):670–4.PubMedCrossRefGoogle Scholar
  20. 20.
    Brown MN et al. Chemoattractant receptors and lymphocyte egress from extralymphoid tissue: changing requirements during the course of inflammation. J Immunol. 2010;185(8):4873–82.PubMedCrossRefGoogle Scholar
  21. 21.
    Schwab SR, Cyster JG. Finding a way out: lymphocyte egress from lymphoid organs. Nat Immunol. 2007;8(12):1295–301.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Edward J. Goetzl
    • 1
    • 2
    • 3
  • Janice B. Schwartz
    • 1
    • 2
  • Mei-Chuan Huang
    • 1
    • 2
  1. 1.Department of MedicineUniversity of California, Geriatric Research CenterSan FranciscoUSA
  2. 2.Department of Microbiology–ImmunologyUniversity of California, Geriatric Research CenterSan FranciscoUSA
  3. 3.University of California, Geriatric Research CenterSan FranciscoUSA

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