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

Abstract

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.