Follicular T helper cells and humoral reactivity in kidney transplant patients

Summary: Memory B cells play a pivotal role in alloreactivity in kidney transplantation. Follicular T helper (Tfh) cells play an important role in the differentiation of B cells into immunoglobulin-producing plasmablasts [through interleukin (IL)-21]. It is unclear to what extent this T cell subset regulates humoral alloreactivity in kidney transplant patients, therefore we investigated the absolute numbers and function of peripheral Tfh cells (CD4POSCXCR5POS T cells) in patients before and after transplantation. In addition, we studied their relationship with the presence of donor-specific anti-human leucocyte antigen (HLA) antibodies (DSA), and the presence of Tfh cells in rejection biopsies. After transplantation peripheral Tfh cell numbers remained stable

Alloantibody Generation and Effector Function Following Sensitization To Human Leukocyte Antigen

Allorecognition is the activation of the adaptive immune system to foreign Human Leukocyte Antigen (HLA) resulting in the generation of alloantibodies. Due to a high polymorphism, foreign HLA is recognized by the immune system following transplant, transfusion or pregnancy resulting in the formation of the germinal center and the generation of long lived alloantibody producing memory B cells. Alloantibodies recognize antigenic epitopes displayed by the HLA molecule on the transplanted allograft and contribute to graft damage through multiple mechanisms including 1) activation of the complement cascade resulting in the formation of the MAC complex and inflammatory anaphylatoxins, 2) transduction of intracellular signals leading to cytoskeletal rearrangement, growth and proliferation of graft vasculature, and 3) immune cell infiltration into the allograft via FcR interactions with the FC portion of the antibody. This review focuses on the generation of HLA alloantibody, routes of sensitization, alloantibody specificity and mechanisms of antibody-mediated graft damage