Portal de Periódicos da CAPES

Long lasting elimination of B cells in NZB/W F1 mice can be induced by NZB but not NZW parental CD8 CTL. (143.12)

2010; American Association of Immunologists; Volume: 184; Issue: 1_Supplement Linguagem: Inglês

10.4049/jimmunol.184.supp.143.12

1550-6606

Charles S. Via, Irina Puliaeva, Kateryna Soloviova, Maksym Puliaiev, Roman Puliaiev,

Systemic Lupus Erythematosus Research

Abstract B cells are a target in current lupus therapy. In the parent-into-F1 (P->F1) model of induced murine lupus, lupus is prevented by donor anti-host cytotoxic T lymphocytes (CTL) elimination of B cells. To determine the therapeutic feasibility of CTL in a spontaneous lupus model, we transferred NZB or NZW parental splenocytes (60 or 90 x 106 cells) into 8 week old female NZB/W F1 mice. 2 weeks after transfer, NZB->F1 mice exhibited significant host B cell reduction and upregulation of B cell Fas consistent with in vivo CTL activity, better seen at the higher dose. By contrast, neither dose of NZW donor cells induced elimination of host B cells below control despite significant donor CD4/CD8 T cell engraftment and donor CD4 upregulation of CD44. At 12 weeks after transfer, NZB->F1 mice exhibited persistent reduction of host B cells significantly below control at both doses whereas B cells were not eliminated in NZW->F1 mice at either dose. No mice developed proteinuria >2+. Thus, NZW splenocytes fail to induce detectable B cell elimination short or long term despite engraftment and activation of donor T cells, indicative of defective effector CTL function. In contrast, NZB->F1 mice support the feasibility of CD8 CTL induction and B cell elimination both short and long term. Studies are in progress to determine if lupus-like disease is also attenuated. If so, more narrowly targeted CD8 CTL may be useful in selectively targeting pathogenic B cells in lupus.