IL-7 increases both thymic-dependent and thymic-independent T-cell regeneration after bone marrow transplantation.
Thymic-dependent differentiation of bone marrow (BM)-derived progenitors and thymic-independent antigen-driven peripheral expansion of mature T cells represent the 2 primary pathways for T-cell regeneration. These pathways are interregulated such that peripheral T-cell expansion is increased in thymectomized versus thymus-bearing hosts after bone marrow transplantation (BMT). This study shows that this interregulation is due to competition between progeny of these 2 pathways because depletion of thymic progeny leads to increased peripheral expansion in thymus-bearing hosts. To test the hypothesis that competition for growth factors modulates the magnitude of antigen-driven peripheral expansion during immune reconstitution in vivo, a variety of T-cell active cytokines were administered after BMT. Of the cytokines (interleukins) tested (IL-3, IL-12, IL-6, IL-2, and IL-7), IL-2 modestly increased peripheral expansion in the face of increasing numbers of thymic emigrants, whereas IL-7 potently accomplished this. This report also demonstrates that the beneficial effect of IL-7 on immune reconstitution is related to both increases in thymopoiesis as well as a direct increase in the magnitude of antigen-driven peripheral expansion. Therefore, the administration of exogenous IL-7, and to a lesser extent IL-2, abrogates the down-regulation in antigen-driven peripheral expansion that occurs in thymus-bearing hosts after BMT. These results suggest that one mechanism by which T-cell-depleted hosts may support antigen-driven T-cell expansion in vivo is via an increased availability of T-cell-active cytokines to support clonal expansion.
Mackall
C L
CL
Pediatric Oncology Branch and Experimental Immunology Branch, National Cancer Institute, Bethesda, MD, USA. cm35c@nih.gov
Fry
T J
TJ
Bare
C
C
Morgan
P
P
Galbraith
A
A
Gress
R E
RE
D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods*; D002454:Cell Differentiation / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology; D005260:Female; D006410:Hematopoiesis / Q000187:drug effects; D015851:Interleukin-7 / Q000494:pharmacology* / Q000502:physiology; D017493:Leukocyte Common Antigens / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012038:Regeneration / Q000187:drug effects; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D013950:Thymus Gland / Q000187:drug effects / Q000276:immunology*; D014185:Transplantation, Isogeneic; D015854:Up-Regulation / Q000187:drug effects
D016207:Cytokines; D015851:Interleukin-7; D017493:Leukocyte Common Antigens