A study of lymphocyte functions in multiple myelopma

University dissertation from Stockholm : Karolinska Institutet, Department of Medicine

Abstract: Multiple myeloma (MM) is a lymphoproliferative disorder which is characterized by an accumulation of clonotypic plasma, cells in the bone marrow leading to an overproduction of monoclonal immunoglobulin (mIg). The disease often implies a poor prognosis. lg-reactive T-cells in MM have been described previously and lg- and dendritic cell (DC)-based immunotherapies in order to elicit and-rumour activity have been attempted in MM. DCs are efficient antigen presenting cells and important in both innate and adaptive immunity. The present study aimed at investigating lymphocyte functions underlying immune mechanisms associated with MM. In the first part of the study we show that mature monocyte-derived DCS from MM patients are susceptible to autologous natural killer (NK,) cell lysis. When NK cells were activated with lower concentrations of IL-2, NK cell-mediated lysis was significantly higher as compared with NK lysis from controls, thus suggesting that DCs in MM patients may be prone to recognition and eradication by NK cells. The second part of the study focuses on specific T-cell immunity in MM. DCs loaded with mIg was cocultured with autologous T-cells and the proliferation was monitored over time. The results show a proliferation of CD4+ T-cells in response to mIg-loaded antigen presenting cells, which could be for most cases inhibited with anti-DR blocking antibody, indicating a MHC class II-restricted response. The cytokine pattern showed negative or low levels of INF-gamma production and varying and enhanced levels of IL4, IL-6 and/or IL10, which suggests a lack of T helper (Th) type 1 activation and a tendency to a Th2 polarization. These observations point to immunoregulatory mechanisms in MM which may be of importance for iminunotherapies.

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