Administration of recombinant human IL-7 to mice alters the composition of B-lineage cells and T cell subsets, enhances T cell function, and induces regression of established metastases.
These studies investigate the effects of exogenously administered recombinant human IL-7 (rhIL-7) on mouse leukocyte subsets in vivo in normal and tumor-bearing mice. The administration of rhIL-7 to normal mice caused a pronounced leukocytosis (three- to fivefold increase over background) in the spleen and lymph nodes, with B-lineage and T cells, NK cells, and macrophages all being increased. CD8+ T cells increased disproportionately, such that the CD4 to CD8 ratio decreased dramatically. The rhIL-7-induced effects were dose-dependent, increased with duration of treatment, and were reversible after cessation of rhIL-7 administration. T cell number increases after rhIL-7 treatment were primarily a result of an expansion of the peripheral T cell population. Importantly, splenocytes from rhIL-7-treated mice have enhanced proliferative responses to various T cell stimuli in vitro and were able to potentiate an allogeneic CTL response in vivo. The rhIL-7-induced changes in T cell number and the CD4 to CD8 ratio also were observed in mice bearing early Renca renal adenocarcinoma pulmonary metastases, and these changes coincided with up to a 75% reduction in pulmonary metastases. Overall, these results demonstrate that the administration of rhIL-7 to mice profoundly increases the number of B and T cells, and reduces the number of pulmonary metastases. The results also suggest that IL-7 may be useful for restoring lymphoid subsets in immunosuppressed hosts and in enhancing T cell-mediated immune responses. Such effects may be useful in the treatment of microbial diseases and cancer.
Komschlies
K L
KL
Biological Carcinogenesis and Development Program, Program Resources, Inc./DynCorp, Frederick, MD 21702.
Gregorio
T A
TA
Gruys
M E
ME
Back
T C
TC
Faltynek
C R
CR
Wiltrout
R H
RH
D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology*; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000556:secondary / Q000628:therapy; D003602:Cytotoxicity, Immunologic; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D015851:Interleukin-7 / Q000008:administration & dosage / Q000494:pharmacology*; D007680:Kidney Neoplasms / Q000276:immunology / Q000556:secondary / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis / Q000276:immunology*; D010641:Phenotype; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D013154:Spleen / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D000943:Antigens, Differentiation; D015851:Interleukin-7; D011994:Recombinant Proteins