Effects of B cell depletion on T cell allogeneic immune responses: a strategy to reduce allogeneic sensitization.
BACKGROUND
B cell depletion has been employed to treat antibody-mediated organ transplantation rejection, although the effects on cellular immune responses have not been extensively investigated.


METHODS
A model of B cell depletion used SCID/beige mice reconstituted with BALB/c splenocytes either depleted of B cells (BD) or not (BN). BD and B/N mice received C57BL/6 skin grafts and were sacrificed after 6 weeks (BD-S6 and BN-S6).


RESULTS
Recall proliferative responses of BD-S6 splenocytes to C57BL/6 were significantly reduced compared to BN-S6, and central memory T cells' proportions (CD4(+)CD44(+)CD62L(+) or CD8(+)CD44(+)CD62L(+)) were significantly decreased in BD-S6 spleens. Recall IFN-gamma production by BD-S6 splenocytes was significantly reduced compared to BN-S6 splenocytes (p=0.0028). Survival times of C57BL/6 heart grafts were significantly longer in SCID/beige mice reconstituted with BD-S6 splenocytes (8.5+/-1.1 days) than for SCID/beige reconstituted with BN-S6 splenocytes (6.0+/-1.1 days; p=0.0006). Under cyclosporine therapy, C57BL/6 heart survival was significantly longer for SCID/beige reconstituted with BD-S6 splenocytes (17.5+/-6.4 days) than those reconstituted with BN-S6 splenocytes (6.2+/-1.5 days; p<0.0001).


CONCLUSIONS
B cell depletion during allogeneic sensitization decreased memory T cells and recalls IFN-gamma production and reduced second-set allograft rejection.
Tsai
Meng-Kun
MK
Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
Chien
Hsiung-Fei
HF
Tzeng
Mei-Ching
MC
Lee
Po-Huang
PH
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D006084:Graft Rejection / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D007156:Immunologic Memory; D007165:Immunosuppression Therapy; D007371:Interferon-gamma / Q000378:metabolism; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D016038:Skin Transplantation; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018183:Transplantation Chimera; D019172:Transplantation Conditioning
D015703:Antigens, CD; D007371:Interferon-gamma