Impaired contact hypersensitivity in macrophage migration inhibitory factor-deficient mice.
To determine whether macrophage migration inhibitory factor (MIF) is required for contact hypersensitivity (CHS) response, MIF-deficient (MIF KO) and wild-type (WT) mice were sensitized with trinitrochlorobenzene (TNCB) or oxazolone on their abdominal skin and challenged on the dorsum skin of one ear 5 days later. Significant ear swelling was observed in the WT mice, but this response was inhibited in the MIF KO mice (p<0.01 for MIF KO vs. WT mice in 24 h). In addition, lymph node cells from hapten-sensitized MIF KO mice showed a decreased capacity for transferring the CHS response. A topical application of TNCB (200 microg) caused a significant decline in epidermal Langerhans cell (LC) density (20.3%; p<0.01 compared with vehicle) 4 h after application in WT mice, but it failed to provoke a significant epidermal LC migration in MIF KO mice (7.4%). By mixed lymphocyte reaction, the T cell proliferative response to alloantigen was significantly decreased in the MIF KO mice compared with WT mice (p<0.005). Taken together, these results indicate that MIF is pivotal in the regulation of cutaneous immune responses and plays a central role in LC migration and T cell proliferation for the CHS response.
Shimizu
Tadamichi
T
Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Abe
Riichiro
R
Nishihira
Jun
J
Shibaki
Akihiko
A
Watanabe
Hirokazu
H
Nakayama
Toshinori
T
Taniguchi
Masaru
M
Ishibashi
Teruo
T
Shimizu
Hiroshi
H
D000287:Administration, Topical; D019264:Adoptive Transfer; D000818:Animals; D002634:Chemotaxis, Leukocyte; D003436:Croton Oil / Q000633:toxicity; D017449:Dermatitis, Allergic Contact / Q000276:immunology*; D004487:Edema / Q000209:etiology; D004817:Epidermis / Q000276:immunology* / Q000473:pathology; D005260:Female; D006241:Haptens / Q000008:administration & dosage / Q000276:immunology; D007106:Immune Sera; D007074:Immunoglobulin G / Q000276:immunology; D007509:Irritants / Q000633:toxicity; D007519:Isoantigens / Q000276:immunology; D007801:Langerhans Cells / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008263:Macrophage Migration-Inhibitory Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010081:Oxazolone / Q000008:administration & dosage / Q000276:immunology; D010853:Picryl Chloride / Q000008:administration & dosage / Q000276:immunology; D011817:Rabbits; D013047:Specific Pathogen-Free Organisms
D006241:Haptens; D007106:Immune Sera; D007074:Immunoglobulin G; D007509:Irritants; D007519:Isoantigens; D008263:Macrophage Migration-Inhibitory Factors; D010081:Oxazolone; D003436:Croton Oil; D010853:Picryl Chloride