Interleukin 15 is a potent stimulant of intraepithelial lymphocytes

Background & Aims: This study examined the effects of interleukin (IL)-15 on intraepithelial lymphocytes (IELs) because they resemble memory cells that react to IL-15 and are located next to epithelial cells that produce IL-15, Methods: Proliferative responses were measured by [H-3]thymidine uptake; interferon (lFN)-gamma production by enzyme-linked immunosorbent assay; and cytotoxicity production by lysis of Cr-51-labeled HT-29 cells. Results: The proliferative response of IELs was much greater with IL-15 than with equivalent amounts of IL-2 or IL-7 (P < 0.001); the same level of blastogenesis was induced by 10(3)-fold less IL-15 than IL-2. Production of IFN-gamma was also highest when IELs were stimulated with IL-15, IELs lysed more Cr-51- labeled HT-29 cells when cultured for 72 hours with IL-15 (48% +/- 3% at 25:1 effector-to-target ratio) than with IL-2 (27% +/- 3%) or IL-7 (12% +/- 2%) (P < 0.0001), Similarly, limiting dilution analysis revealed a greater frequency of cytotoxic precursors in IELs that were stimulated by IL-15 rather than IL-2: 1/467 vs. 1/1900, But IL-15 did not alter the number of natural killer cells, as determined by quantitating CD16 and CD56 by immunofluorescence. Rather, it increased serine esterase content in IELs, Conclusions: IL-15 is the most potent of the known cytokines for IELs, inducing the highest levels of proliferation, IFN-gamma production, and cytotoxicity.