CD8+ T cells from CLL patients show increased production of IFNγ and TNFα, and increased expression of TBET, but normal production of IL2. Cytokine production by CD8+ T cells was assessed by intracytoplasmic staining for IFNγ, TNFα, and IL2 after stimulation with PMA and ionomycin. CD8+ T cells from CLL patients showed increased production of IFNγ (A) and TNFα (B) reflecting the global skew toward CD8+CCR7− subsets (TEM and TEMRA). (C) In contrast, there was no significant difference in the production of IL2 by CD8+ T cells from patients and controls. (D) CD160 was expressed on CD8+ T cells that produced IFNγ but not on cells producing IL4, consistent with its expression being restricted to Tc1 cells. (E) The expression of TBET in CD8+ T-cell subsets from CLL patients was analyzed as defined by coexpression of CCR7 and CD45RA as before. The expression of TBET was increased in TEM cells, with the highest expression levels in the TEMRA subset. (F) CD3+CD8+CCR7− T cells from patients with CLL show significantly increased TBET expression compared with controls.