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 (> or =60 years) and in MGUS patients, when compared to younger controls. PBL from MGUS 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/CD8alpha) augmented anti-CD3 inducible IL-6 production similarly in both groups. However, MGUS PBL also produced measurable IL-6 when activated with sCD30L/CD8alpha 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.
Ellis
T M
TM
Division of Hematology/Oncology, Loyola University School of Medicine, Maywood, Illinois 60153, USA.
Le
P T
PT
DeVries
G
G
Stubbs
E
E
Fisher
M
M
Bhoopalam
N
N
D000368:Aged; D000375:Aging / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000097:blood; D053285:CD30 Ligand; D016827:CD8 Antigens / Q000502:physiology; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D017730:Ki-1 Antigen / Q000032:analysis* / Q000502:physiology; D008213:Lymphocyte Activation; D008297:Male; D008562:Membrane Glycoproteins / Q000502:physiology; D008875:Middle Aged; D010265:Paraproteinemias / Q000276:immunology*; D013601:T-Lymphocytes / Q000502:physiology*
D000911:Antibodies, Monoclonal; D053285:CD30 Ligand; D016827:CD8 Antigens; D015850:Interleukin-6; D017730:Ki-1 Antigen; D008562:Membrane Glycoproteins; C505774:TNFSF8 protein, human