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  • Title: CD40-independent help by memory CD4 T cells induces pathogenic alloantibody but does not lead to long-lasting humoral immunity.
    Author: Rabant M, Gorbacheva V, Fan R, Yu H, Valujskikh A.
    Journal: Am J Transplant; 2013 Nov; 13(11):2831-2841. PubMed ID: 24102790.
    Abstract:
    CD40/CD154 interactions are essential for productive antibody responses to T-dependent antigens. Memory CD4 T cells express accelerated helper functions and are less dependent on costimulation when compared with naïve T cells. Here, we report that donor-reactive memory CD4 T cells can deliver help to CD40-deficient B cells and induce high titers of IgG alloantibodies that contribute to heart allograft rejection in CD40-/- heart recipients. While cognate interactions between memory helper T and B cells are crucial for CD40-independent help, this process is not accompanied by germinal center formation and occurs despite inducible costimulatory blockade. Consistent with the extrafollicular nature of T/B cell interactions, CD40-independent help fails to maintain stable levels of serum alloantibody and induce differentiation of long-lived plasma cells and memory B cells. In summary, our data suggest that while CD40-independent help by memory CD4 T cells is sufficient to induce high levels of pathogenic alloantibody, it does not sustain long-lasting anti-donor humoral immunity and B cell memory responses. This information may guide the future use of CD40/CD154 targeting therapies in transplant recipients containing donor-reactive memory T cells.
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