title: Human IL-18 receptor and ST2L are stable and selective markers for the respective type 1 and type 2 circulating lymphocytes.
abstract: CD4(+) (Th) and CD8(+) (Tc) T and NK lymphocytes can be divided into type 1 and 2 subsets according to their cytokine secretion profile. Studies on the role of lymphocyte subsets in human diseases have been hampered by the lack of stable surface markers to define them. Recently, we reported that ST2L and IL-18R are stably expressed on murine Th2 and Th1 cells, respectively. In this study, we generated Abs to human homologues of ST2L and IL-18R and tested them against Th1/Th2, Tc1/Tc2, and NK1/NK2 lines and PBMCs from healthy individuals. We show for the first time that ST2L and IL-18R are stable selective cell surface markers for human Th2/Tc2/NK2 and Th1/Tc1/NK1 lymphocytes, respectively. We then investigated PBMCs from HIV-infected patients and HIV-negative individuals, to test whether Abs to these two surface markers could be used directly to monitor lymphocyte subset distribution in human diseases. We found a clear Th1 to Th2 shift in the HIV-infected individuals, thus settling a long-standing controversy and include, for the first time, Tc and NK cells as well. Therefore, these cell surface molecules could serve as important determinants of the immune status of human diseases in general, and thereby could be useful for therapeutic monitoring and intervention.
authors.affiliation: Department of Virology, St. Bartholomew's School of Medicine, Queen Mary Westfield College, University of London, 51-53 Bartholomew Close, London EC1A 7BE, UK. w.l.chan@mds.qmw.ac.uk
authors.forename: W L
authors.initials: WL
authors.lastname: Chan
authors.forename: N
authors.initials: N
authors.lastname: Pejnovic
authors.forename: C A
authors.initials: CA
authors.lastname: Lee
authors.forename: N A
authors.initials: NA
authors.lastname: Al-Ali
mesh_terms: D015415:Biomarkers / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D029941:Fish Proteins; D015658:HIV Infections / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D053727:Interleukin-18 Receptor alpha Subunit; D007694:Killer Cells, Natural / Q000378:metabolism; D037102:Lectins / Q000096:biosynthesis / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008297:Male; D018123:Receptors, Interleukin / Q000096:biosynthesis / Q000378:metabolism*; D053724:Receptors, Interleukin-18; D016176:T-Lymphocyte Subsets / Q000378:metabolism*; D018417:Th1 Cells / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D016207:Cytokines; D029941:Fish Proteins; C508572:IL18R1 protein, human; D053727:Interleukin-18 Receptor alpha Subunit; D037102:Lectins; D018123:Receptors, Interleukin; D053724:Receptors, Interleukin-18; C113695:STL2 protein, Oncorhynchus mykiss