Epidermal langerhans cells are dispensable for humoral and cell-mediated immunity elicited by gene gun immunization.
Gene gun immunization, i.e., bombardment of skin with DNA-coated particles, is an efficient method for the administration of DNA vaccines. Direct transfection of APC or cross-presentation of exogenous Ag acquired from transfected nonimmune cells enables MHC-I-restricted activation of CD8(+) T cells. Additionally, MHC-II-restricted presentation of exogenous Ag activates CD4(+) Th cells. Being the principal APC in the epidermis, Langerhans cells (LC) seem ideal candidates to accomplish these functions. However, the dependence on LC of gene gun-induced immune reactions has not yet been demonstrated directly. This was primarily hampered by difficulties to discriminate the contributions of LC from those of other dermal dendritic cells. To address this problem, we have used Langerin-diphtheria toxin receptor knockin mice that allow for selective inducible ablation of LC. LC deficiency, even over the entire duration of experiments, did not affect any of the gene gun-induced immune functions examined, including proliferation of CD4(+) and CD8(+) T cells, IFN-gamma secretion by spleen cells, Ab production, CTL activity, and development of protective antitumor immunity. Together, our data show that gene gun immunization is capable of inducing humoral and cell-mediated immune reactions independently of LC.
Stoecklinger
Angelika
A
Christian Doppler Laboratory of Allergy Diagnostics and Therapy, Department of Molecular Biology, University Salzburg, Salzburg, Austria.
Grieshuber
Ines
I
Scheiblhofer
Sandra
S
Weiss
Richard
R
Ritter
Uwe
U
Kissenpfennig
Adrien
A
Malissen
Bernard
B
Romani
Nikolaus
N
Koch
Franz
F
Ferreira
Fatima
F
Thalhamer
Josef
J
Hammerl
Peter
P
D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D019470:Biolistics; D019496:Cancer Vaccines / Q000008:administration & dosage; D049109:Cell Proliferation; D000078404:Epidermal Cells; D004817:Epidermis / Q000276:immunology*; D005434:Flow Cytometry; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D007111:Immunity, Cellular; D007114:Immunization / Q000379:methods*; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma / Q000378:metabolism; D007801:Langerhans Cells / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental / Q000276:immunology / Q000517:prevention & control; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage
D019496:Cancer Vaccines; C587883:HBEGF protein, human; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D011956:Receptors, Cell Surface; D019444:Vaccines, DNA; D007371:Interferon-gamma