The differential effect of alloantigen-blocking antibodies on unprimed and memory T helper cells

Responsiveness to recall antigens by memory and naive T helper cells is different. To study whether such a difference is also applicable to affinity for allorecognition, we analyzed the effect of an IgG MLR blocking antibody separated from sera of patients with known kidney transplant chronic rejection on primed and unprimed CD4+ T cell alloreactivity. The results show that addition of the IgG fraction inhibits the patient's own unprimed T helper cell responses to a panel of four different alloantigens as well as a third-party mixed lymphocyte response. The same IgG fraction inhibited third-party naive T helper cell, but not autologous unprimed T helper cell, proliferation to adherent anti-CD3 antibody, which suggests that the mechanism of inhibitory action of the IgG is allogeneic-dependent. This IgG also did not induce inhibition of any of the T helper cell clone responsiveness, raised from the same or other patients, when stimulated with the same alloantigens used for unprimed cell alloactivation. Differential responses of naive and memory CD4+ T cells to alloantigens may explain some differences between the in vivo and in vitro systems and why allograft rejection can proceed in the presence of allogeneic blocking antibodies.