T-CELL REPERTOIRE IN PATIENTS WITH MULTIPLE-MYELOMA AND MONOCLONAL GAMMOPATHY OF UNDETERMINED SIGNIFICANCE - CLONAL CD8(-CELL EXPANSIONS ARE FOUND PREFERENTIALLY IN PATIENTS WITH A LOW TUMOR BURDEN() T)

The T cell receptor (TCR) variable (V) gene repertoire was analyzed in patients with monoclonal gammopathy of undetermined significance (MGU S) (n = 17), multiple myeloma (MM) stage I (n = 16), MM stages II/III (n = 31) and age-matched controls (n = 27) by immunofluorescence and f low cytometry using a panel of mouse monoclonal antibodies (mAb) (n = 10) against TCR V alpha and V beta gene products. T cell expansion was defined as a value 1 thrice the normal median value for each respecti ve TCR V mAb. Fifty-three percent of all patients displayed CD8(+) exp ansion(s) as compared to 30% of age-matched controls (p < 0.001). With in the CD4 subset, 18% of the patients displayed T cell expansion(s) i n comparison to 11% of the controls (not significant). Interestingly, the CD8(+) expansion(s) were more frequently noted in patients with a low tumor burden (MGUS/MMI) (73%) as compared to those with advanced d isease (MM II/III) (32% and control donors (30%) (p < 0.01). Likewise, multiple CD8(+) expansions (two or more) were more common in MGUS/MM I patients than in MM II/III and controls (p < 0.01). The T cell expan sions were stable over time in patients with a stable disease. A high degree of clonality of the expansions was detected by TCR CDR3 fragmen t length analysis, determination of J beta gene usage and nucleotide s equencing. The frequent finding of oligoclonal CD8(+) T cell expansion s in patients with a low tumor mass, but not in patients with advanced disease justifies further work in order to identify the relevance of expanded CD8(+) T cells. In one patient with T cell reactivity against the autologous myeloma idiotype, two expansions within the CD8 popula tion (V beta 3 and V beta 5.2 respectively) displayed no reactivity ag ainst the idiotype. Instead, idiotype recognition was confined to a CD 8 non-expanded V beta 22(+) T cell population, with a highly restricte d TCR usage (CDR3 fragment length analysis).