B cell depletion in murine lupus using cytotoxic T lymphocytes in vivo: Feasibility and benefit

• Published in: Cellular immunology Vol. 353; p. 104117
• Main Authors: Soloviova, Kateryna, Puliaeva, Irina, Puliaiev, Maksym, Puliaev, Roman, Via, Charles S.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01-07-2020
• Subjects: Animals; Autoantibodies - immunology; Autoimmunity - immunology; B-Lymphocytes - immunology; Disease Models, Animal; Feasibility Studies; Female; Graft-vs.-host disease; Lupus; Lupus Erythematosus, Systemic - immunology; Lupus Erythematosus, Systemic - therapy; Male; Mice; Mice, Inbred NZB; Parent-into-F1; T cells; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Cytotoxic - metabolism; Graft-vs.-host disease; Lupus; NZB/NZW F1; graft -vs.-host disease; cGVHD; used: aGVHD; T cells; Parent-into-F1; p→F1
• ISSN: 0008-8749; 1090-2163
• DOI: 10.1016/j.cellimm.2020.104117

•B cell depleting agents show promise in human lupus.•The parent-into-F1 model induces B cell depletion by CD8 CTL in vivo.•NZB transfers into B/W (NZBàF1) hosts induces significant B cell elimination.•NZW → F1 mice exhibited mild transient B cell elimination.•Surprisingly, only NZW → F1 mice exhibited improved lupus and survival.
Given the promising results in human lupus with B cell depletion, we tested whether in vivo cytotoxic T lymphocyte (CTL) could eliminate autoreactive B cells in the setting of murine lupus. Using the parent-into-F1 (P → F1) model to generate CTL that eliminate B cells, we found that transfer ofNZB parental splenocytes into lupus-prone female NZB/W F1 mice resulted in profound B cell reduction whereas NZW → F1 mice exhibited defective B cell elimination. Using pre-disease or early disease B/W mice as hosts, NZB → F1 mice exhibited B cell depletion and improved proteinuria but no improvement in survival whereas NZW → F1 mice had significantly reduced proteinuria and prolonged survival. Thus, despite the defective IL-2 environment in B/W F1 mice, generation of CTL and B cell depletion is feasible in NZB → F1 mice. The surprising increase in survival for NZW → F1 mice despite defective B cell elimination suggests that NZW splenocytes may contain a beneficial down regulatory cell.