Administration of rhIL-7 in humans increases in vivo TCR repertoire diversity by preferential expansion of naive T cell subsets

Journal of Experimental Medicine

Volumn 205, Issue 7, 2008, Pages 1701-1714

  Sportès, Claude ^a   Hakim, Frances T ^a   Memon, Sarfraz A ^a   Zhang, Hua ^b   Chua, Kevin S ^b   Brown, Margaret R ^d   Fleisher, Thomas A ^d   Krumlauf, Michael C ^a   Babb, Rebecca R ^a   Chow, Catherine K ^c   Fry, Terry J ^b   Engels, Julie ^e   Buffet, Renaud ^e   Morre, Michel ^e   Amato, Robert J ^f   Venzon, David J ^g   Korngold, Robert ^h   Pecora, Andrew ^h   Gress, Ronald E ^a   Mackall, Crystal L ^b  

^a Experimental Transplantation and Immunology Branch   (United States)

^b NATIONAL CANCER INSTITUTE   (United States)

^c Department of Radiology ^*  (United States)

^d NATIONAL INSTITUTES OF HEALTH   (United States)

^e Cytheris Inc   (France)

^f HOUSTON METHODIST HOSPITAL   (United States)

^g National Cancer Institute   (United States)

^h HACKENSACK UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

INTERLEUKIN 7 RECEPTOR ALPHA; PROTEIN BCL 2; RECOMBINANT INTERLEUKIN 7; T LYMPHOCYTE RECEPTOR; TRANSCRIPTION FACTOR FOXP3;

ADULT; AGED; AGING; ARTICLE; BIODIVERSITY; CANCER IMMUNOTHERAPY; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELL MIGRATION; CLINICAL ARTICLE; CLINICAL STUDY; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DOSE RESPONSE; DRUG BLOOD LEVEL; DRUG DOSE ESCALATION; DRUG DOSE TITRATION; DRUG EFFECT; DRUG WITHDRAWAL; FEMALE; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS; HYPERTENSION; IMMUNE RESPONSE; IN VIVO STUDY; LYMPHOCYTE DEPLETION; LYMPHOCYTE PROLIFERATION; MAXIMUM TOLERATED DOSE; MULTIPLE CYCLE TREATMENT; NEOPLASM; PHASE 1 CLINICAL TRIAL; PHYSIOLOGY; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; PROTEIN EXPRESSION; REGULATORY T LYMPHOCYTE; SPLEEN SIZE; T LYMPHOCYTE; THORAX PAIN; THYMUS; TREATMENT RESPONSE; UPREGULATION;

AGE FACTORS; ANIMALS; CD4 LYMPHOCYTE COUNT; CD8-POSITIVE T-LYMPHOCYTES; FEMALE; HIV; HIV INFECTIONS; HUMANS; INTERLEUKIN-7; LYMPHOCYTE DEPLETION; MALE; MICE; NEOPLASMS; PROTO-ONCOGENE PROTEINS C-BCL-2; RECEPTORS, ANTIGEN, T-CELL; RECOMBINANT PROTEINS; T-LYMPHOCYTES, REGULATORY; UP-REGULATION;

EID: 46949105036     PISSN: 00221007     EISSN: 00221007     Source Type: Journal    
DOI: 10.1084/jem.20071681     Document Type: Article

References (52)

1. Blattman, J.N., J.M. Grayson, E.J. Wherry, S.M. Kaech, K.A. Smith, and R. Ahmed. 2003. Therapeutic use of IL-2 to enhance antiviral T cell responses in vivo. Nat. Med. 9:540-547.
2. Khan, I.A., and L. Casciotti. 1999. IL-15 prolongs the duration of CD8+ T cell-mediated immunity in mice infected with a vaccine strain of Toxoplasma gondii. J. Immunol. 163:4503-4509.
3. Berzofsky, J.A., J.D. Ahlers, J. Janik, J. Morris, S. Oh, M. Terabe, and I.M. Belyakov. 2004. Progress on new vaccine strategies against chronic viral infections. J. Clin. Invest. 114:450-462.
4. Wang, L.X., R. Li, G. Yang, M. Lim, A. O ' Hara, Y. Chu, B.A. Fox, N.P. Restifo, W.J. Urba, and H.M. Hu. 2005. Interleukin-7-dependent expansion and persistence of melanoma-specific T cells in lymphodepleted mice lead to tumor regression and editing. Cancer Res. 65:10569-10577.
5. + T cell expansion and function. J. Exp. Med. 201:139-148.
6. Klebanoff, C.A., S.E. Finkelstein, D.R. Surman, M.K. Lichtman, L. Gattinoni, M.R. Theoret, N. Grewal, P.J. Spiess, P.A. Antony, D.C. Palmer, et al. 2004. IL-15 enhances the in vivo antitumor activity of tumor-reactive CD8+ T cells. Proc. Natl. Acad. Sci. USA. 101:1969-1974.
7. Park, J.H., Q. Yu, B. Erman, J.S. Appelbaum, D. Montoya-Durango, H.L. Grimes, and A. Singer. 2004. Suppression of IL7Ralpha transcription by IL-7 and other prosurvival cytokines: a novel mechanism for maximizing IL-7-dependent T cell survival. Immunity. 21:289-302.
8. Grabstein, K.H., T.J. Waldschmidt, F.D. Finkelman, B.W. Hess, A.R. Alpert, N.E. Boiani, A.E. Namen, and P.J. Morrissey. 1993. Inhibition of murine B and T lymphopoiesis in vivo by an anti-interleukin 7 monoclonal antibody. J. Exp. Med. 178:257-264.
9. von Freeden-Jeffry, U., P. Vieira, L.A. Lucian, T. McNeil, S.E. Burdach, and R. Murray. 1995. Lymphopenia in interleukin (IL)-7 gene-deleted mice identifies IL-7 as a nonredundant cytokine. J. Exp. Med. 181:1519-1526.
10. Murray, R., T. Suda, N. Wrighton, F. Lee, and A. Zlotnik. 1989. IL-7 is a growth and maintenance factor for mature and immature thymocyte subsets. Int. Immunol. 1:526-531.
11. Puel, A., S.F. Ziegler, R.H. Buckley, and W.J. Leonard. 1998. Defective IL7R expression in T(-)B(+)NK(+) severe combined immunodeficiency. Nat. Genet. 20:394-397.
12. Noguchi, M., H. Yi, H.M. Rosenblatt, A.H. Filipovich, S. Adelstein, W.S. Modi, O.W. McBride, and W.J. Leonard. 1993. Interleukin-2 receptor gamma chain mutation results in X-linked severe combined immunodeficiency in humans. Cell. 73:147-157.
13. Schluns, K.S., W.C. Kieper, S.C. Jameson, and L. Lefrancois. 2000. Interleukin-7 mediates the homeostasis of naive and memory CD8 T cells in vivo. Nat. Immunol. 1:426-432.
14. Fry, T.J., E. Connick, J. Falloon, M.M. Lederman, D.J. Liewehr, J. Spritzler, S.M. Steinberg, L.V. Wood, R. Yarchoan, J. Zuckerman, et al. 2001. A potential role for interleukin-7 in T cell homeostasis. Blood. 97:2983-2990.
15. Napolitano, L.A., R.M. Grant, S.G. Deeks, D. Schmidt, S.C. De Rosa, L.A. Herzenberg, B.G. Herndier, J. Andersson, and J.M. McCune. 2001. Increased production of IL-7 accompanies HIV-1-mediated T cell depletion: implications for T cell homeostasis. Nat. Med. 7:73-79.
16. Bolotin, E., G. Annett, R. Parkman, and K. Weinberg. 1999. Serum levels of IL-7 in bone marrow transplant recipients: relationship to clinical characteristics and lymphocyte count. Bone Marrow Transplant. 23:783-788.
17. Mackall, C.L., T.J. Fry, C. Bare, P. Morgan, A. Galbraith, and R.E. Gress. 2001. IL-7 increases both thymic-dependent and thymic-independent T cell regeneration after bone marrow transplantation. Blood. 97:1491-1497.
18. Beq, S., M.T. Nugeyre, R. Ho Tsong Fang, D. Gautier, R. Legrand, N. Schmitt, J. Estaquier, F. Barre-Sinoussi, B. Hurtrel, R. Cheynier, and N. Israel. 2006. IL-7 induces immunological improvement in SIV-infected rhesus macaques under antiviral therapy. J. Immunol. 176:914-922.
19. Fry, T.J., M. Moniuszko, S. Creekmore, S.J. Donohue, D.C. Douek, S. Giardina, T.T. Hecht, B.J. Hill, K. Komschlies, J. Tomaszewski, et al. 2003. IL-7 therapy dramatically alters peripheral T cell homeostasis in normal and SIV-infected nonhuman primates. Blood. 101:2294-2299.
20. Storek, J., T. Gillespy III, H. Lu, A. Joseph, M.A. Dawson, M. Gough, J. Morris, R.C. Hackman, P.A. Horn, G.E. Sale, et al. 2003. Interleukin-7 improves CD4 T cell reconstitution after autologous CD34 cell transplantation in monkeys. Blood. 101:4209-4218.
21. Melchionda, F., T.J. Fry, M.J. Milliron, M.A. McKirdy, Y. Tagaya, and C.L. Mackall. 2005. Adjuvant IL-7 or IL-15 overcomes immunodominance and improves survival of the CD8+ memory cell pool. J. Clin. Invest. 115:1177-1187.
22. Li, B., M.J. Vanroey, and K. Jooss. 2007. Recombinant IL-7 enhances the potency of GM-CSF-secreting tumor cell immunotherapy. Clin. Immunol. 123:155-165.
23. Ernst, B., D.S. Lee, J.M. Chang, J. Sprent, and C.D. Surh. 1999. The peptide ligands mediating positive selection in the thymus control T cell survival and homeostatic proliferation in the periphery. Immunity. 11:173-181.
24. Goldrath, A.W., and M.J. Bevan. 1999. Low-affinity ligands for the TCR drive proliferation of mature CD8+ T cells in lymphopenic hosts. Immunity. 11:183-190.
25. Chu, Y.W., S.A. Memon, S.O. Sharrow, F.T. Hakim, M. Eckhaus, P.J. Lucas, and R.E. Gress. 2004. Exogenous IL-7 increases recent thymic emigrants in peripheral lymphoid tissue without enhanced thymic function. Blood. 104:1110-1119.
26. Seddiki, N., B. Santner-Nanan, J. Martinson, J. Zaunders, S. Sasson, A. Landay, M. Solomon, W. Selby, S.I. Alexander, R. Nanan, et al. 2006. Expression of interleukin (IL)-2 and IL-7 receptors discriminates between human regulatory and activated T cells. J. Exp. Med. 203:1693-1700.
27. + T reg cells. J. Exp. Med. 203:1701-1711.
28. Rosenberg, S.A., C. Sportes, M. Ahmadzadeh, T.J. Fry, L.T. Ngo, S.L. Schwarz, M. Stetler-Stevenson, K.E. Morton, S.A. Mavroukakis, M. Morre, et al. 2006. IL-7 administration to humans leads to expansion of CD8+ and CD4+ cells but a relative decrease of CD4+ T-regulatory cells. J. Immunother. 29:313-319.
29. Mackall, C.L. 2000. T cell immunodeficiency following cytotoxic anti-neoplastic therapy: a review. Stem Cells. 18:10-18.
30. Hakim, F.T., S.A. Memon, R. Cepeda, E.C. Jones, C.K. Chow, C. Kasten-Sportes, J. Odom, B.A. Vance, B.L. Christensen, C.L. Mackall, and R.E. Gress. 2005. Age-dependent incidence, time course, and consequences of thymic renewal in adults. J. Clin. Invest. 115:930-939.
31. Sportes, C., N.J. McCarthy, F. Hakim, S.M. Steinberg, D.J. Liewehr, D. Weng, S. Kummar, J. Gea-Banacloche, C.K. Chow, R.M. Dean, et al. 2005. Establishing a platform for immunotherapy: clinical outcome and study of immune reconstitution after high-dose chemotherapy with progenitor cell support in breast cancer patients. Biol. Blood Marrow Transplant. 11:472-483.
32. Akashi, K., M. Kondo, U. von Freeden-Jeffry, R. Murray, and I.L. Weissman. 1997. Bcl-2 rescues T lymphopoiesis in interleukin-7 receptor-deficient mice. Cell. 89:1033-1041.
33. Hofmeister, R., A.R. Khaled, N. Benbernou, E. Rajnavolgyi, K. Muegge, and S.K. Durum. 1999. Interleukin-7: physiological roles and mechanisms of action. Cytokine Growth Factor Rev. 10:41-60.
34. Sereti, I., H. Imamichi, V. Natarajan, T. Imamichi, M.S. Ramchandani, Y. Badralmaa, S.C. Berg, J.A. Metcalf, B.K. Hahn, J.M. Shen, et al. 2005. In vivo expansion of CD4CD45RO-CD25 T cells expressing foxP3 in IL-2-treated HIV-infected patients. J. Clin. Invest. 115:1839-1847.
35. Zhang, H., K.S. Chua, M. Guimond, V. Kapoor, M.V. Brown, T.A. Fleisher, L.M. Long, D. Bernstein, B.J. Hill, D.C. Douek, et al. 2005. Lymphopenia and interleukin-2 therapy alter homeostasis of CD4+CD25+ regulatory T cells. Nat. Med. 11:1238-1243.
36. Ahmadzadeh, M., and S.A. Rosenberg. 2006. IL-2 administration increases CD4+ CD25(hi) Foxp3+ regulatory T cells in cancer patients. Blood. 107:2409-2414.
37. Kovacs, J.A., M. Baseler, R.J. Dewar, S. Vogel, R.T. Davey Jr., J. Falloon, M.A. Polis, R.E. Walker, R. Stevens, N.P. Salzman, et al. 1995. Increases in CD4 T lymphocytes with intermittent courses of interleukin-2 in patients with human immunodeficiency virus infection. A preliminary study. N. Engl. J. Med. 332:567-575.
38. Kovacs, J.A., S. Vogel, J.A. Metcalf, M. Baseler, R. Stevens, J. Adelsberger, R. Lempicki, R.L. Hengel, I. Sereti, L. Lambert, et al. 2001. Interleukin-2 induced immune effects in human immunodeficiency virus-infected patients receiving intermittent interleukin-2 immunotherapy. Eur. J. Immunol. 31:1351-1360.
39. Hassan, J., and D.J. Reen. 2001. Human recent thymic emigrants- identification, expansion, and survival characteristics. J. Immunol. 167:1970-1976.
40. Kaech, S.M., J.T. Tan, E.J. Wherry, B.T. Konieczny, C.D. Surh, and R. Ahmed. 2003. Selective expression of the interleukin 7 receptor identifies effector CD8 T cells that give rise to long-lived memory cells. Nat. Immunol. 4:1191-1198.
41. Kim, H.R., M.S. Hong, J.M. Dan, and I. Kang. 2006. Altered IL-7Ralpha expression with aging and the potential implications of IL-7 therapy on CD8+ T cell immune responses. Blood. 107:2855-2862.
42. Rethi, B., C. Fluur, A. Atlas, M. Krzyzowska, F. Mowafi, S. Grutzmeier, A. De Milito, R. Bellocco, K.I. Falk, E. Rajnavolgyi, and F. Chiodi. 2005. Loss of IL-7Ralpha is associated with CD4 T cell depletion, high interleukin-7 levels and CD28 down-regulation in HIV infected patients. AIDS. 19:2077-2086.
43. Douek, D.C., R.A. Vescio, M.R. Betts, J.M. Brenchley, B.J. Hill, L. Zhang, J.R. Berenson, R.H. Collins, and R.A. Koup. 2000. Assessment of thymic output in adults after haematopoietic stem-cell transplantation and prediction of T cell reconstitution. Lancet. 355:1875-1881.
44. Broers, A.E., S.J. Posthumus-van Sluijs, H. Spits, B. van der Holt, B. Lowenberg, E. Braakman, and J.J. Cornelissen. 2003. Interleukin-7 improves T cell recovery after experimental T cell-depleted bone marrow transplantation in T cell-deficient mice by strong expansion of recent thymic emigrants. Blood. 102:1534-1540.
45. Mackall, C.L., T.A. Fleisher, M.R. Brown, M.P. Andrich, C.C. Chen, I.M. Feuerstein, M.E. Horowitz, I.T. Magrath, A.T. Shad, S.M. Steinberg, et al. 1995. Age, thymopoiesis, and CD4+ T-lymphocyte regeneration after intensive chemotherapy. N. Engl. J. Med. 332:143-149.
46. Hakim, F.T., and R.E. Gress. 2005. Reconstitution of the lymphocyte compartment after lymphocyte depletion: a key issue in clinical immunology. Eur. J. Immunol. 35:3099-3102.
47. Benigni, F., V.S. Zimmermann, S. Hugues, S. Caserta, V. Basso, L. Rivino, E. Ingulli, L. Malherbe, N. Glaichenhaus, and A. Mondino. 2005. Phenotype and homing of CD4 tumor-specific T cells is modulated by tumor bulk. J. Immunol. 175:739-748.
48. Klebanoff, C.A., L. Gattinoni, and N.P. Restifo. 2006. CD8+ T cell memory in tumor immunology and immunotherapy. Immunol. Rev. 211:214-224.
49. Pawelec, G., S. Koch, C. Gouttefangeas, and A. Wikby. 2006. Immunorejuvenation in the elderly. Rejuvenation Res. 9:111-116.
50. Sallusto, F., J. Geginat, and A. Lanzavecchia. 2004. Central memory and effector memory T cell subsets: function, generation, and maintenance. Annu. Rev. Immunol. 22:745-763.
51. Currier, J.R., H. Deulofeut, K.S. Barron, P.J. Kehn, and M.A. Robinson. 1996. Mitogens, superantigens, and nominal antigens elicit distinctive patterns of TCRB CDR3 diversity. Hum. Immunol. 48:39-51.
52. Puisieux, I., J. Even, C. Pannetier, F. Jotereau, M. Favrot, and P. Kourilsky. 1994. Oligoclonality of tumor-infiltrating lymphocytes from human melanomas. J. Immunol. 153:2807-2818.