Programmed death-1 (PD-1), a member of the CD28 costimulatory receptor family, is expressed by germinal center-associated T cells in reactive lymphoid tissue. In a study of a wide range of lymphoproliferative disorders, neoplastic T cells in 23 cases of angioimmunoblastic lymphoma were immunoreactive for PD-1, but other subtypes of T cell and B cell non-Hodgkin lymphoma, as well as classic Hodgkin lymphoma, did not express PD-1. The pattern of PD-1 immunostaining of neoplastic cells in angioimmunoblastic lymphoma was similar to that reported for CD10, a recently described marker of neoplastic T cells in angioimmunoblastic lymphoma. Tumor-associated follicular dendritic cells in cases of angioimmunoblastic lymphoma were found to express PD-L1, the PD-1 ligand. In addition, PD-1-positive reactive T cells formed rosettes around neoplastic L&H cells in 14 cases of nodular lymphocyte predominant Hodgkin lymphoma studied. These findings, along with data from previous studies, suggest that angioimmunoblastic lymphoma is a neoplasm of germinal center-associated T cells and that there is an association of germinal center-associated T cells and neoplastic cells in nodular lymphocyte predominant Hodgkin lymphoma. PD-1 is a useful new marker for angioimmunoblastic lymphoma and lends further support to a model of T-cell lymphomagenesis in which specific subtypes of T cells may undergo neoplastic transformation and result in specific, distinct histologic, immunophenotypic, and clinical subtypes of T-cell neoplasia.

Complement is a central effector system within the immune system and is implicated in a range of inflammatory disorders. CD59 is a key regulator of complement membrane attack complex (MAC) assembly. The atherogenic role of terminal complement has long been suspected, but is still unclear. Here, we demonstrate that among mice deficient in apolipoprotein E (Apoe), the additional loss of murine CD59 (mCd59ab−/−/Apoe−/−) accelerated advanced atherosclerosis featuring occlusive coronary atherosclerosis, vulnerable plaque, and premature death, and that these effect could be attenuated by over-expression of human CD59 in the endothelium. Complement inhibition using a neutralizing anti-mouse C5 antibody attenuated atherosclerosis in mCd59ab−/−/Apoe−/− mice. Furthermore, MAC mediated endothelial damage and promoted foam cell formation. These combined results highlight the atherogenic role of MAC and the athero-protective role of CD59, and suggest that inhibition of MAC formation may provide a therapeutic approach for the treatment of atherosclerosis.