Differential roles of interleukin 15 mRNA isoforms generated by alternative splicing in immune responses in vivo.
At least two types of interleukin (IL)-15 mRNA isoforms are generated by alternative splicing at the 5' upstream of exon 5 in mice. To elucidate the potential roles of IL-15 isoforms in immune responses in vivo, we constructed two groups of transgenic mice using originally described IL-15 cDNA with a normal exon 5 (normal IL-15 transgenic [Tg] mice) and IL-15 cDNA with an alternative exon 5 (alternative IL-15 Tg mice) under the control of an MHC class I promoter. Normal IL-15 Tg mice constitutionally produced a significant level of IL-15 protein and had markedly increased numbers of memory type (CD44(high) Ly6C(+)) of CD8(+) T cells in the LN. These mice showed resistance to Salmonella infection accompanied by the enhanced interferon (IFN)-gamma production, but depletion of CD8(+) T cells exaggerated the bacterial growth, suggesting that the IL-15-dependent CD8(+) T cells with a memory phenotype may serve to protect against Salmonella infection in normal IL-15 Tg mice. On the other hand, a large amount of intracellular IL-15 protein was detected but hardly secreted extracellularly in alternative IL-15 Tg mice. Although most of the T cells developed normally in the alternative IL-15 Tg mice, they showed impaired IFN-gamma production upon TCR engagement. The alternative IL-15 transgenic mice were susceptible to Salmonella accompanied by impaired production of endogenous IL-15 and IFN-gamma. Thus, two groups of IL-15 Tg mice may provide information concerning the different roles of IL-15 isoforms in the immune system in vivo.
Nishimura
H
H
Laboratory of Host Defense & Germfree Life, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Nagoya 466, Japan. nishihit@med.nagoya-u.ac.jp
Yajima
T
T
Naiki
Y
Y
Tsunobuchi
H
H
Umemura
M
M
Itano
K
K
Matsuguchi
T
T
Suzuki
M
M
Ohashi
P S
PS
Yoshikai
Y
Y
D017398:Alternative Splicing; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D019409:Interleukin-15 / Q000235:genetics / Q000502:physiology*; D007376:Interleukin-2 / Q000494:pharmacology; D008198:Lymph Nodes / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D020033:Protein Isoforms / Q000502:physiology; D012333:RNA, Messenger / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012481:Salmonella Infections, Animal / Q000276:immunology
D016207:Cytokines; D019409:Interleukin-15; D007376:Interleukin-2; D020033:Protein Isoforms; D012333:RNA, Messenger