Expression of L-selectin on Th1 cells is regulated by IL-12.
L-selectin has become established as a key molecule in the recirculation of naïve T cells from the blood to peripheral lymph nodes, yet little is known about its role in the migration of effector or memory cells. While differentiating naïve CD4+ T cells into Th1 and Th2 subsets in vitro, it was noted that L-selectin levels were maintained on the Th1 subset of cells. The expression of L-selectin on the Th1 cells appeared to be dependent on the presence of IL-12. Th2 cells, differentiated in the absence of IL-12, failed to maintain L-selectin expression. Coculture with IL-12, IL-18, IL-4, TNF-alpha, or IFN-alpha, -beta, or -gamma demonstrated a dependence on IL-12 alone for L-selectin expression. In addition, the inclusion of heat-killed Listeria monocytogenes in the cultures also maintained L-selectin expression on the Th1 cells. In all cultures, the maintenance of L-selectin on the T cell surface could be blocked by the inclusion of anti-IL-12 Abs. Analysis of the mRNA levels for L-selectin in T cells, differentiated in the presence or absence of IL-12, showed that the cytokine appears to exert its effect on L-selectin at the transcriptional level. Given the key role played by IL-12 in the differentiation of naïve T cells into the Th1 subset, the observation that IL-12 can also regulate L-selectin expression has implications for the migration of Th1 effector cells both through the lymphatic system and to sites of inflammation.
van Wely
C A
CA
Immunology Unit, Glaxo Wellcome Medicines Research Centre, Stevenage, United Kingdom. cavw14089@glaxowellcome.co.uk
Beverley
P C
PC
Brett
S J
SJ
Britten
C J
CJ
Tite
J P
JP
D000276:Adjuvants, Immunologic / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D006358:Hot Temperature; D018664:Interleukin-12 / Q000502:physiology*; D019041:L-Selectin / Q000096:biosynthesis* / Q000235:genetics; D008089:Listeria monocytogenes / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000096:biosynthesis; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D018418:Th2 Cells / Q000378:metabolism; D014158:Transcription, Genetic / Q000276:immunology
D000276:Adjuvants, Immunologic; D012333:RNA, Messenger; D019041:L-Selectin; D018664:Interleukin-12