In:
The Journal of Immunology, The American Association of Immunologists, Vol. 192, No. 1_Supplement ( 2014-05-01), p. 202.27-202.27
Abstract:
After allogeneic hematopoietic cell transplantation, donor-derived T cells can attack host tumor cells, producing a favorable graft-vs.-tumor (GVT) effect. However, graft-vs.-host disease (GVHD) may develop when donor T cells attack normal host tissue. We previously reported that while granzyme B (GzmB) is required for CD8+ T cells to cause GVHD, GzmB-mediated damage of CD8+ T cells impairs the GVT effect. In this study, we examined the role of GzmB in GVT and GVHD mediated by CD4+ T cell subsets, using an established A20 tumor model and bioluminescence imaging to monitor tumor growth in BALB/c hosts. We found that CD4+CD25+ regulatory T cells (Tregs) derived from C57BL/6 donors significantly suppressed GVT activity mediated by both CD8+ T cells and CD4+CD25- effector T cells (Teffs). However, GzmB-/- Tregs were as equally suppressive as WT Tregs, consistent with our previous report that GzmB is not required for Treg-mediated suppression of GVHD. Nonetheless, GzmB-/- Teffs were less effective in controlling tumor growth than WT Teffs; but surprisingly, GzmB-/- Teffs caused more severe GVHD than WT Teffs. Our data reveal that GzmB is essential for CD4+CD25- Teff-mediated optimal GVT effect but diminishes the ability of Teffs to cause GVHD, which contradicts its role in CD8+ T cells where GzmB is essential to cause GVHD but impairs GVT effect. These differential roles suggest that targeting GzmB in selected T cell subsets may provide a strategy to separate GVT from GVHD.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.192.Supp.202.27
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2014
detail.hit.zdb_id:
1475085-5
