Contrasting effects of B cell depletion on CD4(+) and CD8(+) memory T cell responses generated after transplantation

B细胞耗竭对移植后产生的CD4(+)和CD8(+)记忆T细胞反应的不同影响

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Abstract

Alloreactive memory T cells play a key role in transplantation by accelerating allograft rejection and preventing tolerance induction. Some studies using µMT mice, which are constitutionally devoid of B cells, showed that B cells were required for the generation of memory T cells after allotransplantation. However, whether B cell depletion in normal adult mice has the same effect on memory responses by CD4(+) and CD8(+) T cells activated after transplantation has not been thoroughly investigated. In this study, we tested the effect of anti-CD20 antibody-mediated B cell depletion on CD4(+) and CD8(+) memory T cell alloresponses after skin transplantation in wild-type mice. We found that B cell depletion prevented the development of memory alloresponses by CD4(+) T cells but enhanced that of CD8(+) memory T cells. Next, we tested the influence of B cell depletion on hematopoietic chimerism. In OT-II CD4(+) anti-OVA TCR transgenic mice sensitized to ovalbumin antigen, B cell depletion also impaired allospecific memory T cell responses and thereby enhanced donor hematopoietic chimerism and T cell deletion after bone marrow transplantation. This study underscores the complexity of the relationships between B and T cells in the generation and reactivation of different memory T cell subsets after transplantation.

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