长效IL-7在人源化淋巴细胞减少症小鼠模型中恢复T细胞重建

Background: Idiopathic CD4 lymphocytopenia (ICL) is a clinical syndrome characterized by low CD4 T-cell counts (<300 cells/μL), occasionally accompanied by CD8 lymphopenia. ICL, which is associated with serious opportunistic infections, cancers, and autoimmune diseases, has no established treatment. Objective: We tested NT-I7 (efineptakin alfa), a long-acting form of recombinant human (rh) IL-7, as a potential immunotherapy for ICL in a preclinical mouse model. Methods: Mice received peripheral blood mononuclear cells from 15 individuals: 5 healthy donors and 10 persons with ICL. Mice receiving ICL cells were either untreated or treated with a single NT-I7 dose. Blood was sampled at different times, and spleens were collected on day 28 to compare lymphocyte reconstitution, IL-7Rα expression, and TCR clonality, while weight was monitored to detect potential graft-versus-host disease. In a single patient study, NT-I7 was administered, and blood lymphocytes were enumerated up to 98 days. Results: In mice that phenocopied their donors' lymphopenia, NT-I7 treatment restored CD4 T-cell counts to the levels observed in mice receiving lymphocytes from healthy donors. A single NT-I7 dose downregulated IL-7Rα on CD4-T cells for 2 to 3 weeks and increased T-cell counts with preserved polyclonality in 3 of 4 patients tested, without causing graft-versus-host disease. The lymphopenic NT-I7-treated patient experienced a 2- and 3-fold rise in CD4 and CD8-T cell numbers, respectively, 2 months after a single dose of NT-I7. Conclusion: A single dose of NT-I7 restored T-cell numbers in a mouse model of ICL and improved lymphocyte counts in a single-patient study.