title: Distinct dacryoadenitides autoadoptively transferred to rabbits by different subpopulations of lymphocytes activated ex vivo.
abstract: OBJECTIVE
  To test whether CD4+ T cells proliferate in mixed cell reactions with autologous lacrimal gland (LG) acinar cells and whether these cells can autoadoptively transfer disease.
  
  
  METHODS
  Purified acinar cells were gamma irradiated and cocultured with peripheral blood lymphocytes. Activated CD4+ T cells were sorted by fluorescence-activated cell sorting (FACS). Unfractionated activated peripheral blood lymphocytes (UF), CD4+-enriched and CD4+-depleted T cells from an autologous mixed cell reaction were injected into the donor rabbit's remaining LG. After 4 weeks, ocular examinations were performed, and the rabbits were euthanized; LGs were removed for histopathology, immunohistochemistry, and real-time reverse transcription-polymerase chain reaction studies.
  
  
  RESULTS
  CD4 T cells increased in the autologous mixed cell reaction from 20% to 80%. Tear production decreased in the induced disease/UF (ID/UF) group and declined even more in the ID/CD4+-enriched group. Tear breakup times decreased and rose bengal staining increased in all groups. All LGs exhibited significant histopathology and increased messenger RNAs for tumor necrosis factor α. The ID/UF group exhibited the largest increases of CD4+ and rabbit T-lymphocyte antigen-positive cells. The ID/CD4+-enriched group contained fewer infiltrating CD4 cells but more eosinophils, severely altered acinar morphology, and increased fibrosis. LG of the ID/CD4+-depleted group exhibited large increases of CD18, major histocompatibility complex II, and CD4+ cells. Messenger RNAs for interleukin 2, interleukin 4, and CD4+ increased in the ID/CD4+-enriched group compared with the CD4+-depleted group.
  
  
  CONCLUSIONS
  Autoreactive CD4+ effector cells activated ex vivo and autoadoptively transferred, caused what seems to be a distinct dacryoadenitis. The CD4+-depleted cell fraction also contained pathogenic effector cells capable of inducing disease.
authors.affiliation: Ocular Surface Center, Doheny Eye Institute, Los Angeles, CA 90033, USA.
authors.forename: Padmaja B
authors.initials: PB
authors.lastname: Thomas
authors.forename: Deedar M
authors.initials: DM
authors.lastname: Samant
authors.forename: Yanru
authors.initials: Y
authors.lastname: Wang
authors.forename: Shivaram
authors.initials: S
authors.lastname: Selvam
authors.forename: Douglas
authors.initials: D
authors.lastname: Stevenson
authors.forename: John D
authors.initials: JD
authors.lastname: Gray
authors.forename: Joel E
authors.initials: JE
authors.lastname: Schechter
authors.forename: Austin K
authors.initials: AK
authors.lastname: Mircheff
authors.forename: Melvin D
authors.initials: MD
authors.lastname: Trousdale
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018920:Coculture Techniques; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003607:Dacryocystitis / Q000276:immunology* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D007124:Immunoenzyme Techniques; D007765:Lacrimal Apparatus / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation / Q000502:physiology*; D007959:Lymphocyte Culture Test, Mixed; D008212:Lymphocyte Depletion; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013666:Tears / Q000378:metabolism
chemical_list: D016207:Cytokines; D012333:RNA, Messenger