Humoral immunity in renal transplantation: clinical significance and therapeutic approach.

Donor-specific antibodies (DSA) form a significant barrier in solid organ transplantation of highly pre-sensitized candidates. Although avoiding transplantation over a positive cross-match test can largely prevent the occurrence of hyperacute antibody-mediated rejection, transplantation of highly pre-sensitized candidates is often complicated by the occurrence of acute and chronic antibody-mediated graft rejection leading to diminished graft function and survival. The pre-existent HLA and/or non-HLA-specific antibodies are without any doubt important contributing factors underlying humoral-mediated graft injury. Furthermore, increasing evidence underlines the association of newly formed de novo DSA after transplantation with poor graft function and survival. There is still a need to further develop desensitizing therapies not only to make transplantation of highly pre-sensitized candidates feasible, but also to reduce the new formation of allo-antibodies. Here, we summarize current views on desensitization therapies and the impact of the presence of DSA on the fate of the kidney graft.

Primary immune responses to human CMV: a critical role for IFN-gamma-producing CD4+ T cells in protection against CMV disease.

The correlates of protective immunity to disease-inducing viruses in humans remain to be elucidated. We determined the kinetics and characteristics of cytomegalovirus (CMV)-specific CD4(+) and CD8(+) T cells in the course of primary CMV infection in asymptomatic and symptomatic recipients of renal transplants. Specific CD8(+) cytotoxic T lymphocyte (CTL) and antibody responses developed regardless of clinical signs. CD45RA(-)CD27(+)CCR7(-) CTLs, although classified as immature effector cells in HIV infection, were the predominant CD8 effector population in the acute phase of protective immune reactions to CMV and were functionally competent. Whereas in asymptomatic individuals the CMV-specific CD4(+) T-cell response preceded CMV-specific CD8(+) T-cell responses, in symptomatic individuals the CMV-specific effector-memory CD4(+) T-cell response was delayed and only detectable after antiviral therapy. The appearance of disease symptoms in these patients suggests that functional CD8(+) T-cell and antibody responses are insufficient to control viral replication and that formation of effector-memory CD4(+) T cells is necessary for recovery of infection.