Previous investigations have demonstrated that an expanding circulating T cell population is able to modulate the malignant clone in multiple myeloma. More recently, an expansion of T cell subsets exhibiting a restricted T cell repertoire has been detected in some MM patients. To further elucidate if 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 reactivity of a panel of monoclonal antibodies specific for different V region families (α or β) in combination with anti-CD4 or anti-CD8, for purified blood T cells from MM patients. TCR V region usage in MM patients was compared to blood T cells from age matched (N = 13) control individuals. The multivariate analysis of variance did not uncover a difference for distribution of TCR V region usage between the normal controls and the MM cohort. However, there were individual MM patients who had expanded T cell with specific 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 region 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 cell subsets within their blood T (CD3+) cells. The stage of disease and treatment status (currently on or off therapy) did not associate with the pattern of restricted T cell repertoire. Finally, a smaller cohort of newly diagnosed, untreated MM patients (N = 13) also demonstrated an expanded T cell repertoire. However, these patients had more CD4 than CD8 cell subsets involved in the altered V region expression in several Vβ families. Thus, these results add to the evidence that this malignant B cell disorder whether newly diagnosed or of longer duration, may be accompanied by an altered T cell repertoire characterized in part by expanded T cell clones.
Bibliographical noteFunding Information:
Keywords: altered T-cell repertoire, CD4-lymphocytes, CD8 lymphocytes, lymphocyte subsets, multiple myeloma, flow cytometry, phenotype This study was conducted by The Eastern Cooperative Oncology Group and supported in part by Public Health Service grants CA15947, CA23318, CA13650, CA20365, CA66636 and CA21115 from the National Cancer Institute, National Institutes of Health, and the Department of Health and Human Services. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute.
Copyright 2018 Elsevier B.V., All rights reserved.
- Altered T-cell repertoire
- CD8 lymphocytes
- Flow cytometry
- Lymphocyte subsets
- Multiple myeloma