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.
Immunology Unit, Glaxo Wellcome Medicines Research Centre, Stevenage, United Kingdom. cavw14089@glaxowellcome.co.uk
C A
CA
van Wely
P C
PC
Beverley
S J
SJ
Brett
C J
CJ
Britten
J P
JP
Tite
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