Stimulation of immune reconstitution by interleukin-7 after syngeneic bone marrow transplantation in mice.
Successful outcome of autologous bone marrow transplantation (BMT) is severely handicapped by susceptibility to infection and by a high rate of relapse. While quantitative aspects of the immune system generally return to normal within the first 3-4 months after BMT, the recovery of qualitative immune functions is prolonged. Since interleukin-7 (IL-7) has growth-promoting and differentiating effects on pre-B cells and immature thymocytes, its role in the recovery of immune functions was investigated in BALB/c mice after syngeneic BMT (sBMT). After sBMT, mice treated with human recombinant IL-7 (rIL-7) showed an 11.9-fold increase in thymic cellularity associated with an enhanced response to a mitogenic stimulus compared with the controls. rIL-7 significantly increased RAG-1 expression and promoted V beta 8(D)J gene rearrangement of the T cell receptor in the thymus. Further, the cytokine boosted survival after challenge with influenza virus following sBMT. The finding that rIL-7 induces differentiation and proliferation of immature thymocytes and counteracts post-BMT immune deficiency makes it a promising medium for clinical application in BMT patients.
Department of Bone Marrow Transplantation, Hadassah University Hospital, Jerusalem, Israel.
A
A
Abdul-Hai
R
R
Or
S
S
Slavin
G
G
Friedman
L
L
Weiss
D
D
Matsa
A
A
Ben-Yehuda
D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology*; D005260:Female; D015870:Gene Expression; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor / Q000187:drug effects; D016654:Genes, RAG-1 / Q000235:genetics; D007107:Immune System / Q000187:drug effects*; D007376:Interleukin-2 / Q000494:pharmacology; D015851:Interleukin-7 / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000517:prevention & control; D011994:Recombinant Proteins / Q000494:pharmacology; D013154:Spleen / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology; D014185:Transplantation, Isogeneic
D007376:Interleukin-2; D015851:Interleukin-7; D011994:Recombinant Proteins