Mouse IL-17: a cytokine preferentially expressed by alpha beta TCR + CD4-CD8-T cells.
A novel cytokine originally designated murine CTLA-8 was described as a cDNA isolated from an activated T cell hybridoma produced by fusing a mouse cytotoxic T cell clone and a rat T lymphoma. This cDNA, which contains mRNA instability sequences characteristic of many cytokines, encoded a putative secreted protein that was homologous to the ORF13 gene of Herpesvirus saimiri. The human homolog to this molecule has recently been identified as the proinflammatory cytokine IL-17. We describe the isolation of a cDNA encoding mouse IL-17 from a cDNA library generated from alpha beta TCR + CD4-CD8- thymocytes using a subtraction technique that enriched for activation specific genes. This cDNA shares 87.3% amino acid identity to the previously described murine CTLA-8. Comparison of murine CTLA-8 to a cDNA we isolated from activated rat splenocytes revealed that murine CTLA-8 is, in fact, the rat homolog of IL-17. Mouse IL-17 mRNA is specifically expressed by activated alpha beta TCR + CD4-CD8- T cells, a small subset with a potentially important role in immune regulation. Mouse, rat, and human IL-17 can induce IL-6 secretion in mouse stromal cells, indicating that all homologs can recognize the mouse receptor.
Kennedy
J
J
Department of Immunology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA 94304, USA.
Rossi
D L
DL
Zurawski
S M
SM
Vega
F
F
Kastelein
R A
RA
Wagner
J L
JL
Hannum
C H
CH
Zlotnik
A
A
D000818:Animals; D001854:Bone Marrow Cells; D003238:Connective Tissue / Q000187:drug effects / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics / Q000302:isolation & purification; D015723:Gene Library; D005796:Genes; D006801:Humans; D020381:Interleukin-17; D015850:Interleukin-6 / Q000378:metabolism; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics* / Q000494:pharmacology; D051379:Mice / Q000235:genetics*; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D051381:Rats; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D016415:Sequence Alignment; D017385:Sequence Homology; D013045:Species Specificity; D013382:Subtraction Technique; D016176:T-Lymphocyte Subsets / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; D020381:Interleukin-17; D015850:Interleukin-6; D007378:Interleukins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011993:Recombinant Fusion Proteins