Alloprimed CD8(+) T cells regulate alloantibody and eliminate alloprimed B cells through perforin- and FasL-dependent mechanisms.
While it is well known that CD4(+) T cells and B cells collaborate for antibody production, our group previously reported that CD8(+) T cells down-regulate alloantibody responses following transplantation. However, the exact mechanism involved in CD8(+) T cell-mediated down-regulation of alloantibody remains unclear. We also reported that alloantibody production is enhanced when either perforin or FasL is deficient in transplant recipients. Here, we report that CD8(+) T cell-deficient transplant recipient mice (high alloantibody producers) exhibit an increased number of primed B cells compared to WT transplant recipients. Furthermore, CD8(+) T cells require FasL, perforin and allospecificity to down-regulate posttransplant alloantibody production. In vivo CD8-mediated clearance of alloprimed B cells was also FasL- and perforin-dependent. In vitro data demonstrated that recipient CD8(+) T cells directly induce apoptosis of alloprimed IgG1(+) B cells in co-culture in an allospecific and MHC class I-dependent fashion. Altogether these data are consistent with the interpretation that CD8(+) T cells down-regulate posttransplant alloantibody production by FasL- and perforin-dependent direct elimination of alloprimed IgG1(+) B cells.
Department of Surgery, Comprehensive Transplant Center, The Ohio State University Wexner Medical Center, Columbus, OH.
J M
JM
Zimmerer
T A
TA
Pham
C L
CL
Wright
K J
KJ
Tobin
P B
PB
Sanghavi
S M
SM
Elzein
V M
VM
Sanders
G L
GL
Bumgardner
D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology*; D015153:Blotting, Western; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D053222:Fas Ligand Protein / Q000378:metabolism*; D005434:Flow Cytometry; D022781:Hepatocytes / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D007518:Isoantibodies / Q000276:immunology* / Q000378:metabolism; D016031:Liver Transplantation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D054353:Perforin / Q000378:metabolism*; D014184:Transplantation, Homologous; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D053222:Fas Ligand Protein; D007074:Immunoglobulin G; D007518:Isoantibodies; D014409:Tumor Necrosis Factor-alpha; D054353:Perforin
Alloantibody; B cells; CD8+ T cells; FasL; Perforin