The Expression of T Cell Related Costimulatory Molecules in Multiple Myeloma

Abstract

Presentation of tumour antigen by malignant cells not expressing costimulatory molecules is considered to be a major cause of the failure of the host's immune response against tumours. This study has determined the expression of the B7 family of costimulatory molecules on malignant plasma cells and the expression of the counter receptor molecules, CD28 and CD 152 (CTLA-4), on T cells of patients with multiple myeloma. CD28 expression was present on most CD4 cells but was lower on CD8 cells especially from those patients who also showed evidence of expanded T cell clones (median 40%. z=2.4; p<0.02). CD152 expression was increased in 50% (9/18) of patients with myeloma. CD80 (B7-1) expression was present on the plasma cells of only 1 of 27 samples but CD86 (B7-2) expression within the normal range was present on the plasma cells of 14 of 27 samples. Primitive plasma cells (CD38++ CD45++) had a higher expression of CD86 (median 78%) than mature plasma cells (CD38++ CD45-) (median 19%, z=3.7; p<0.01). Thus patients with expanded T cell clones have a downregulated T cell CD28 expression and lack B7-1 expression on their malignant plasma cells. These results are consistent with the concept that engagement of the T cell receptor by tumour antigen on B7-1 deficient malignant plasma cells would result in T cell anergy rather than productive immunity.

Key Words:

• multiple myeloma
• T cell
• costimulatory molecules
• CD28
• B7-1