CD4 and B-cell chronic lymphocytic leukemia: IL-21 is produced by CD4+ T cells and follicular T cells, and primes CLL cells for proliferation but also renders them more sensitive to apoptosis.3 IL-15 is produced by monocytes and may enhance CLL proliferation and survival.12 IL-2 shares these properties and is primarily produced by CD4+ and CD8+ T cells.13,14 Importantly, CD40 activation upregulates the IL-21, IL-15, and IL-2 receptors,15,16 which may further prime CLL cells for proliferation and survival.