The Journal of Immunology, Vol 146, Issue 5 1547-1552, Copyright © 1991 by American Association of Immunologists

ARTICLES

Administration of IL-7 to mice with cyclophosphamide-induced lymphopenia accelerates lymphocyte repopulation

PJ Morrissey, P Conlon, S Braddy, DE Williams, AE Namen and DY Mochizuki
Immunex Corporation, Seattle, WA 98101.

Lymphopenia was induced in mice by a single injection of cyclophosphamide. IL-7 or a control protein were administered to the mice twice daily and the cellularity and composition of the spleen, lymph node, bone marrow, and thymus were determined at various time points thereafter. In comparison to the control cyclophosphamide- treated mice, animals receiving cyclophosphamide and IL-7 had an accelerated regeneration of splenic and lymph node cellularity. There was no significant difference in the rate of recovery of the bone marrow and thymus of the control and IL-7-treated mice. Assessment of the pre-B cell compartment revealed a dramatic increase in total pre-B cell numbers in the spleen and bone marrow of the IL-7-treated mice as measured by both flow microfluorimetry and a pre-B cell colony-forming assay. This was followed in a few days by a significant increase in surface IgM+B cell numbers to levels above normal values in both the spleen and lymph node. IL-7 administration to cyclophosphamide-treated mice also resulted in an accelerated recovery of peripheral CD4+ and CD8+ cell numbers in the spleen and lymph node. The numbers of CD8+ cells were increased by twofold over normal levels in cyclophosphamide- treated mice receiving IL-7. Myeloid recovery was determined in cyclophosphamide treated mice by assessing the numbers of CFU- granulocyte-macrophage and Mac 1+ cells. There was no significant difference in myeloid recovery between cyclophosphamide-treated mice receiving IL-7 or control protein. These results suggest that administration of IL-7 after chemical-induced lymphopenia may have therapeutic benefits in shortening the period required to achieve normal lymphoid cellularity.

This article has been cited by other articles:

				O. Boyman, C. Ramsey, D. M. Kim, J. Sprent, and C. D. Surh IL-7/Anti-IL-7 mAb Complexes Restore T Cell Development and Induce Homeostatic T Cell Expansion without Lymphopenia J. Immunol., June 1, 2008; 180(11): 7265 - 7275. [Abstract] [Full Text] [PDF]

				G. L. Goldberg, O. Alpdogan, S. J. Muriglan, M. V. Hammett, M. K. Milton, J. M. Eng, V. M. Hubbard, A. Kochman, L. M. Willis, A. S. Greenberg, et al. Enhanced Immune Reconstitution by Sex Steroid Ablation following Allogeneic Hemopoietic Stem Cell Transplantation J. Immunol., June 1, 2007; 178(11): 7473 - 7484. [Abstract] [Full Text] [PDF]

				L. Swainson, S. Kinet, C. Mongellaz, M. Sourisseau, T. Henriques, and N. Taylor IL-7-induced proliferation of recent thymic emigrants requires activation of the PI3K pathway Blood, February 1, 2007; 109(3): 1034 - 1042. [Abstract] [Full Text] [PDF]

				L. Swainson, E. Verhoeyen, F.-L. Cosset, and N. Taylor IL-7R{alpha} Gene Expression Is Inversely Correlated with Cell Cycle Progression in IL-7-Stimulated T Lymphocytes. J. Immunol., June 1, 2006; 176(11): 6702 - 6708. [Abstract] [Full Text] [PDF]

				A. Audige, E. Schlaepfer, H. Joller, and R. F. Speck Uncoupled Anti-HIV and Immune-Enhancing Effects when Combining IFN-{alpha} and IL-7 J. Immunol., September 15, 2005; 175(6): 3724 - 3736. [Abstract] [Full Text] [PDF]

				J. J. Lum, D. J. Schnepple, Z. Nie, J. Sanchez-Dardon, G. L. Mbisa, J. Mihowich, N. Hawley, S. Narayan, J. E. Kim, D. H. Lynch, et al. Differential Effects of Interleukin-7 and Interleukin-15 on NK Cell Anti-Human Immunodeficiency Virus Activity J. Virol., June 1, 2004; 78(11): 6033 - 6042. [Abstract] [Full Text] [PDF]

				L. A. Napolitano, C. A. Stoddart, M. B. Hanley, E. Wieder, and J. M. McCune Effects of IL-7 on Early Human Thymocyte Progenitor Cells In Vitro and in SCID-hu Thy/Liv Mice J. Immunol., July 15, 2003; 171(2): 645 - 654. [Abstract] [Full Text] [PDF]

				N. Dainiak, J. K. Waselenko, J. O. Armitage, T. J. MacVittie, and A. M. Farese The Hematologist and Radiation Casualties Hematology, January 1, 2003; 2003(1): 473 - 496. [Abstract] [Full Text] [PDF]

				T. J. Fry and C. L. Mackall Interleukin-7: from bench to clinic Blood, May 13, 2002; 99(11): 3892 - 3904. [Full Text] [PDF]

				A. M. Farese, D. B. Casey, W. G. Smith, R. M. Vigneulle, J. P. McKearn, and T. J. MacVittie Leridistim, a Chimeric Dual G-CSF and IL-3 Receptor Agonist, Enhances Multilineage Hematopoietic Recovery in a Nonhuman Primate Model of Radiation-Induced Myelosuppression: Effect of Schedule, Dose, and Route of Administration Stem Cells, November 1, 2001; 19(6): 522 - 533. [Abstract] [Full Text]

				O. Alpdogan, C. Schmaltz, S. J. Muriglan, B. J. Kappel, M.-A. Perales, J. A. Rotolo, J. A. Halm, B. E. Rich, and M. R. M. van den Brink Administration of interleukin-7 after allogeneic bone marrow transplantation improves immune reconstitution without aggravating graft-versus-host disease Blood, October 1, 2001; 98(7): 2256 - 2265. [Abstract] [Full Text] [PDF]

				T. J. Fry, B. L. Christensen, K. L. Komschlies, R. E. Gress, and C. L. Mackall Interleukin-7 restores immunity in athymic T-cell-depleted hosts Blood, March 15, 2001; 97(6): 1525 - 1533. [Abstract] [Full Text] [PDF]

				C. L. Mackall, T. J. Fry, C. Bare, P. Morgan, A. Galbraith, and R. E. Gress IL-7 increases both thymic-dependent and thymic-independent T-cell regeneration after bone marrow transplantation Blood, March 1, 2001; 97(5): 1491 - 1497. [Abstract] [Full Text] [PDF]

				C. L. Mackall, D. Stein, T. A. Fleisher, M. R. Brown, F. T. Hakim, C. V. Bare, S. F. Leitman, E. J. Read, C. S. Carter, L. H. Wexler, et al. Prolonged CD4 depletion after sequential autologous peripheral blood progenitor cell infusions in children and young adults Blood, July 15, 2000; 96(2): 754 - 762. [Abstract] [Full Text] [PDF]

				U. Kapp, M. Bhatia, D. Bonnet, B. Murdoch, and J. E. Dick Treatment of Non-Obese Diabetic (NOD)/Severe-Combined Immunodeficient Mice (SCID) With flt3 Ligand and Interleukin-7 Impairs the B-Lineage Commitment of Repopulating Cells After Transplantation of Human Hematopoietic Cells Blood, September 15, 1998; 92(6): 2024 - 2031. [Abstract] [Full Text] [PDF]

				F Young, B Ardman, Y Shinkai, R Lansford, T K Blackwell, M Mendelsohn, A Rolink, F Melchers, and F W Alt Influence of immunoglobulin heavy- and light-chain expression on B-cell differentiation. Genes & Dev., May 1, 1994; 8(9): 1043 - 1057. [Abstract] [PDF]