Altered T cell repertoire usage in CD4 and CD8 subsets of multiple myelomapatients, a study of the Eastern Cooperative Oncology Group (E9487)

Previous investigations have demonstrated that an expanding circulating T c ell population is able to modulate the malignant clone in multiple myeloma. More recently, an expansion of T cell subsets exhibiting a restricted T ce ll repertoire has been detected in some MM patients. To further elucidate i f a selected T cell expansion occurs in MM, we studied the T cell receptor (TCR) variable (V) region expression from a cohort of previously diagnosed and treated MM patients (N=37). The latter was done by assessing the reacti vity of a panel of monoclonal antibodies specific for different V region fa milies (alpha or beta) in combination with anti-CD4 or anti-CD8, for purifi ed blood T cells from MM patients. TCR V region usage in MM patients was co mpared to blood T cells from age matched (N=13) control individuals. The mu ltivariate analysis of variance did not uncover a difference for distributi on of TCR V region usage between the normal controls and the MM cohort. How ever, there were individual MM patients who had expanded T cells with speci fic TCR V region expression when compared to the control group. Several MM patients had multiple, expanded CD4 and/or CD8 subsets based on TCR V regio n expression. The majority of MM patients had expanded T cell subsets that constituted less than 10% of the total blood T cell pool. However, a few MM patients (N=3) had larger percentages (range 34-84%) of these expanded T c ell subsets within their blood T (CD3+) cells. The stage of disease and tre atment status (currently on or off therapy) did not associate with the patt ern of restricted T cell repertoire. Finally, a smaller cohort of newly dia gnosed, untreated MM patients (N=13) also demonstrated an expanded T cell r epertoire. However, these patients had more CD4 than CD8 cell subsets invol ved in the altered V region expression in several VP families. Thus, these results add to the evidence that this malignant B cell disorder whether new ly diagnosed or of longer duration, may be accompanied by an altered T cell repertoire characterized in part by expanded T cell clones.