title: Shedding New Light on the Process of "Licensing" for Pathogenicity by Th Lymphocytes.
abstract: Th cells sensitized against autoantigens acquire pathogenicity following two sequential events, namely activation by their target Ag and a process named "licensing." In this study, we analyzed these processes in a transgenic mouse system in which TCR-transgenic Th cells specific to hen egg lysozyme (HEL) are adoptively transferred to recipients and induce inflammation in eyes expressing HEL. Our data show that the notion that the lung is the organ where "licensing" for pathogenicity takes place is based on biased data collected with cells injected i.v., a route in which most transferred cells enter via the lung. Thus, we found that when donor cells were activated in vitro and injected intraperitoneally, or were activated in vivo, they migrated simultaneously to the lung, spleen, and other tested organs. In all, tested organs donor cells undergo "licensing" for pathogenicity, consisting of vigorous increase in number and changes in expression levels of inflammation-related genes, monitored by both flow cytometry and microarray analysis. After reaching peak numbers, around day 3, the "licensed" donor cells migrate to the circulation and initiate inflammation in the HEL-expressing recipient eyes. Importantly, the kinetics of increase in number and of changes in gene expression by the donor cells were similar in lung, spleen, and other tested organs of the recipient mice. Furthermore, the total numbers of donor cells in the spleen at their peaks were 10- to 100-fold larger in the spleen than in the lung, contradicting the notion that the lung is the organ where "licensing" takes place.
authors.affiliation: Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Cuiyan
authors.identifier: 0000-0001-8151-4051
authors.initials: C
authors.lastname: Tan
authors.affiliation: Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Wambui S
authors.identifier: 0000-0002-6254-7429
authors.initials: WS
authors.lastname: Wandu
authors.affiliation: Genetic Engineering Core, National Eye Institute, National Institutes of Health, Bethesda, MD 20892; and.
authors.forename: R Steven
authors.identifier: 0000-0003-0836-5314
authors.initials: RS
authors.lastname: Lee
authors.affiliation: Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Samuel H
authors.identifier: 0000-0002-3322-3492
authors.initials: SH
authors.lastname: Hinshaw
authors.affiliation: Cancer and Inflammation Program, National Cancer Institute, National Institutes of Health, Frederick, MD 21702.
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Klinman
authors.affiliation: Genetic Engineering Core, National Eye Institute, National Institutes of Health, Bethesda, MD 20892; and.
authors.forename: Eric
authors.identifier: 0000-0003-2959-911X
authors.initials: E
authors.lastname: Wawrousek
authors.affiliation: Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892; geryi@nei.nih.gov.
authors.forename: Igal
authors.initials: I
authors.lastname: Gery
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D008168:Lung / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D009113:Muramidase / Q000276:immunology; D013154:Spleen / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
chemical_list: D001324:Autoantigens; C421864:hen egg lysozyme; D009113:Muramidase