title: IL-15 promotes survival but not effector function differentiation of CD8+ TCRalphabeta+ intestinal intraepithelial lymphocytes.
abstract: CD8 single-positive cells, including CD8alphaalpha+ and CD8alphabeta+ subsets, constitute the majority of TCRalphabeta+ intestinal intraepithelial lymphocytes (alphabeta iIEL) in mice. CD8+ alphabeta iIEL show significantly weaker responses to TCR stimulation in the presence of exogenous IL-2 than do CD8+ T cells of the central immune system. IL-15 is a T cell growth factor likely expressed in the intestine mucosa. To understand the role of IL-15 in CD8+ alphabeta iIEL biology, we compared the effects of exogenous IL-15 and IL-2 on the survival and primary responses of the two CD8+ alphabeta iIEL subsets in vitro. In contrast to the death of approximately 60% of both CD8alphaalpha+ and CD8alphabeta+ iIEL cultured in IL-2 with or without TCR stimulation, IL-15 promoted survival of the CD8alphaalpha+ subset in the presence of TCR stimulation and promoted survival of both subsets in the absence of TCR stimulation. The higher proliferation level of TCR stimulated CD8alphaalpha+ alphabeta iIEL cultured in IL-15 compared with those cultured in IL-2 is likely due to IL-15's prosurvival effects. In addition, unlike exogenous IL-2, exogenous IL-15 did not support the effector functions of either iIEL subsets, including IFN-gamma production, IL-4-induced Th2 cytokine production, and anti-TCR mAb-redirected cytotoxicity. These findings demonstrate that IL-15 and IL-2 are functionally distinct and suggest that IL-15 plays a unique role in the maintenance of the CD8+ alphabeta iIEL pool in the absence of Ag stimulation and in the survival and expansion of CD8alphaalpha+ alphabeta iIEL upon Ag stimulation.
authors.affiliation: Institute of Molecular Biology, Academia Sinica, and Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Y G
authors.initials: YG
authors.lastname: Lai
authors.forename: V
authors.initials: V
authors.lastname: Gelfanov
authors.forename: V
authors.initials: V
authors.lastname: Gelfanova
authors.forename: L
authors.initials: L
authors.lastname: Kulik
authors.forename: C L
authors.initials: CL
authors.lastname: Chu
authors.forename: S W
authors.initials: SW
authors.lastname: Jeng
authors.forename: N S
authors.initials: NS
authors.lastname: Liao
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002454:Cell Differentiation; D002470:Cell Survival; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D007371:Interferon-gamma / Q000378:metabolism; D019409:Interleukin-15 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D007422:Intestines / Q000166:cytology / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D016693:Receptors, Antigen, T-Cell, alpha-beta; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology*; D018418:Th2 Cells
chemical_list: D016207:Cytokines; C508025:Il15ra protein, mouse; D019409:Interleukin-15; D007376:Interleukin-2; D016693:Receptors, Antigen, T-Cell, alpha-beta; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2; D015847:Interleukin-4; D007371:Interferon-gamma