Germinal Center B Cells are Uniquely Targeted by Antibody-Suppressor CXCR5CD8 T Cells.

BACKGROUND

Alloprimed antibody-suppressor CXCR5CD8 T cells (CD8 T cells) downregulate alloantibody production, mediate cytotoxicity of IgG B cells, and prolong allograft survival. The purpose of this investigation was to determine which immune-cell subsets are susceptible to CD8 T cell-mediated cytotoxicity or noncytotoxic suppression.

METHODS

Alloprimed immune-cell subsets were evaluated for susceptibility to CD8 T cell-mediated in vitro cytotoxicity and/or suppression of intracellular cytokine expression. In vivo CD8-mediated cytotoxicity to wild-type germinal center (GC) B cells or wild-type CD4 T follicular helper cells (T cells) was assessed in RAG1 knockout mice. The impact of in vivo adoptive transfer of CD8 T cells into hepatocyte or kidney transplant recipients on the quantity of lymphoid immune-cell subsets was assessed.

RESULTS

CD8 T cells mediated allospecific cytotoxicity to alloprimed GC B cells but not alloprimed extrafollicular plasmablasts, marginal zone B cells, follicular B cells, or plasma cells. CD8 T cells did not mediate cytotoxicity to alloprimed dendritic cells, macrophages, CD4 T cells, CD4 T follicular regulatory cells, or CD4 regulatory T cell. CD8 T cells did not suppress CD4 T cell, T follicular regulatory cell, or regulatory T-cell cytokine expression. Adoptive transfer of CD8 T cells into hepatocyte or kidney transplant recipients reduced alloantibody production and the quantity of GC B cells, T cells, and plasma cells (but not other B-cell, T-cell, or antigen-presenting cell subsets). The reduction of T-cell quantity was dependent on CD8 T cell-mediated major histocompatibility complex-I-dependent cytotoxic killing of GC B cells.

CONCLUSIONS

The primary targets of CD8 T cells are GC B cells with downstream reduction of T and plasma cells.