Alterations in CD30+ T cells in monoclonal gammopathy of undetermined significance

Monoclonal gammopathy of unknown significance (MGUS) is a monoclonal B cell expansion characterized by high levels of circulating monoclonal antibody that affects 3% of individuals over the age of 70. Although this is considered benign, a high percentage of MGUS patients develop a debilitating peripheral autoimmune neuropathy and have a significantly increased risk for progression to multiple myeloma, Here we show that the relative numbers of the CD30(+) T cell subset and levels of CD30 expression are elevated in activated lymphocytes from normal aged individuals (greater than or equal to 60 years) and in MGUS patients, when compared to younger controls. PBL from MG;US patients and age-matched controls produced comparable levels of IL-6 when activated with anti-CD3 plus IL-2, and costimulation with a soluble form of CD30 ligand (sCD30L/CD8 alpha) augmented anti-CD3 inducible IL-6 production similarly in both groups. However, MGUS PBL also produced measurable IL-6 when activated with sCD30L/CD8 alpha alone. This capability was associated with the unique presence of CD30(+) T cells in the peripheral blood of MGUS patients. Furthermore, a higher percentage of activated MGUS T cells express CD30 when activated by incubation with idiotype-expressing autologous serum (68 +/- 13) than those activated by anti-CD3 plus IL-2 (43 +/- 7). These results indicate that quantitative alterations in CD30(+) T cells accompany aging and MGUS and that these cells may contribute to the chronic activation of B cells though the production of IL-6. (C) 2001 Academic Press.