title: Numerical, morphological and phenotypic changes in Langerhans cells in the course of murine graft-versus-host disease.
abstract: BACKGROUND
  In the course of graft-versus-host disease (GVHD) or diseases that histologically mimic GVHD (e.g. toxic epidermal necrolysis, Stevens-Johnson syndrome), it is known that epidermal Langerhans cells (LCs) are depleted from the epidermis. However, the mechanism and significance of LC depletion is not well known.
  
  
  OBJECTIVE
  To investigate the numerical, morphological and phenotypic changes in LCs and apoptosis of LCs in the course of GVHD using a non-irradiated mouse GVHD model.
  
  
  METHODS
  BALB/c nu/nu mice and C57BL/6 mice were used as recipients and donors, respectively. Recipient mice were injected with T-cell-enriched donor spleen cells. Skin samples were harvested at various times after the inoculation. The numerical and morphological changes were examined by an immunofluorescence study of epidermal sheets. Apoptosis was studied by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling method and flow cytometric analysis using annexin V. Phenotypic change was studied by flow cytometric analysis of epidermal cell suspensions. The mixed epidermal cell lymphocyte reaction (MELR) was performed to examine functional changes in the epidermal cells.
  
  
  RESULTS
  Five days after inoculation, a graft-versus-host reaction occurred. Epidermal LCs began to decrease from the sixth day. On the fifth day, the LCs became larger and had prominent dendrites. Immediately before the LCs began to decrease, many LCs became round in shape, with scanty dendrites. LC apoptosis was not observed in the epidermis either on the fifth or seventh day. Phenotypically, the expression of CD40, CD80, CD86 and major histocompatibility complex class II antigen on the LCs was upregulated on the fifth and seventh day. Epidermal cells from GVHD mice showed an increased allostimulatory capacity in the secondary MELR.
  
  
  CONCLUSIONS
  These results suggest that at early GVHD onset, most LCs may not undergo apoptosis in the epidermis but are phenotypically activated, resulting in further activation of alloreactive T cells and aggravation of the disease.
authors.affiliation: Department of Dermatology, Okayama University Medical School, Japan. asakoshi@cc.okayama-u.ac.jp
authors.forename: K
authors.initials: K
authors.lastname: Asagoe
authors.forename: K
authors.initials: K
authors.lastname: Takahashi
authors.forename: T
authors.initials: T
authors.lastname: Yoshino
authors.forename: E
authors.initials: E
authors.lastname: Kondo
authors.forename: R
authors.initials: R
authors.lastname: Tanaka
authors.forename: J
authors.initials: J
authors.lastname: Arata
authors.forename: T
authors.initials: T
authors.lastname: Akagi
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis; D002452:Cell Count; D004817:Epidermis / Q000473:pathology; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000473:pathology*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D016130:Immunophenotyping; D007801:Langerhans Cells / Q000276:immunology / Q000473:pathology*; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D010641:Phenotype; D015854:Up-Regulation
chemical_list: D015703:Antigens, CD; D000949:Histocompatibility Antigens Class II