Memory CD4 T cell helps alter isotype and specificity of donor-reactive alloantibody (TRAN3P.894)

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Abstract As alloreactive antibody (alloAb) mediate allograft rejection we tested how memory CD4 T cells influence alloAb responses in a murine renal transplantation model. While A/J (H-2a) kidney allografts are spontaneously accepted by naïve B6 (H-2b) recipients, donor-reactive memory CD4 T cells induced rapid rejection through induction of alloAb. We compared serum titers and isotypes of donor-reactive alloAb and the numbers of plasma cells secreting Ab against individual donor MHC antigens in B6 recipients with or without transfer of polyclonal A/J-primed memory CD4 T cells. As anticipated, recipients containing memory CD4 T cells developed faster and stronger alloAb responses than non-sensitized recipients. However, the effects of memory CD4 T cell help were not limited to the accelerated kinetics and higher magnitude of alloAb production. Memory CD4 T cells induced high titers of IgG2c, IgG2b and IgG1 Ab reactive to A/J. In contrast, anti-donor Ab in non-sensitized recipients were exclusively IgG2b. High numbers of plasma cells secreting Ab against donor MHC class I molecule H-2Dd were detected in recipients containing memory CD4 T cells, but not in non-sensitized recipients. Thus, donor-reactive alloAb induced by memory and naive CD4 T cells differ not only in quantity but also in isotype distribution and specificity that in turn may influence their pathogenicity. These findings underscore the importance of targeting helper functions of donor-reactive memory CD4 T cells.