Tuesday, July 12, 2011

T-cells are important in CLL

Nick Chiorazzi's group have published a paper in Blood that shows a method that enables mature CLL cells to grow in a mouse model. They use a nonobese diabetes/severe combined immunodeficincy/gammacnull mouse into which they introduce precursors of human hematopoietic and mesenchymal lineages. It had been previously found that in order for CLL cells to fail to be rejected by a mouse, it has to be very immuno-incompetent indeed. A NOD/SCID mouse lacks the IL-2 family common cytokine receptor gamma chain gene rendering the animal completely deficient in lymphocytes including NK cells. In addition, CLL cells require the support of T cells, monocytes and monocyte-derived nurse-like cells and stromal cells.

They established that autologous CD3+, CD4+ T cells were necessary for CLL engraftment and proliferation, whereas murine stroma and monocyte-derived lineages are quite sufficient to support growth. Another human cell type that facilitated growth in this model was allogeneic antigen presnting cells (either CD14+ or CD19+). This suggests that activation of T cells in necessary for the facilitation of CLL growth to occur.

It may be that the effectiveness of T-cell toxic drugs like fludarabine and Campath derives from their ability to kill T cells. Possibly the importance of T/B interactions is reflected in some of the epiphenomena of CLL such as second malignancies, immunodeficiency and autoimmunity.

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