ICAM-1 and LFA-1 on mouse epidermal Langerhans cells and spleen dendritic cells identify disparate requirements for activation of KLH-specific CD4+ Th1 and Th2 clones.
Expression of the adhesion molecules ICAM-1 and LFA-1 (CD11a/CD18) on mouse epidermal Langerhans cells (LC) and on spleen dendritic cells (DC) from BALB/c mice was examined by staining with specific mAb and was evaluated by flow cytometry. LC were shown to express both ICAM-1 and LFA-1, whereas spleen DC expressed only LFA-1. The contribution of these adhesion molecules to LC- or DC-induced activation of keyhole limpet hemocyanin (KLH)-specific, Iad-restricted, Th1 or Th2 clones was investigated in mAb blocking studies. At optimal doses, anti-CD11a or anti-CD18 mAb completely inhibited Th1 proliferation induced by either LC or DC. Anti-ICAM-1 also abrogated Th1 proliferation induced by LC, but only moderately reduced Th1 proliferation induced by DC. Inhibition in these experiments was specific, since isotype-matched control Ab against other Ag constitutively expressed on LC (NLDC 145) or DC (33D1) had no effect on Th1 proliferation. In marked contradistinction, the capacity of LC to present KLH to our Th2 clones was resistant to treatment with the same mAb against ICAM-1, CD11a or CD18. We conclude that interactions between ICAM-1 and LFA-1 on epidermal LC and LFA-1 on spleen DC with their respective ligands on our Th1 clones are required for optimal presentation of protein Ag to Th1. Our results also indicate that neither ICAM-1 nor LFA-1 is required for the analogous activation of our Th2 clones by LC.
Simon
J C
JC
Department of Dermatology, University of Texas Southwestern Medical Center, Dallas 75235-9069.
Girolomoni
G
G
Edelbaum
D
D
Bergstresser
P R
PR
Cruz
P D
PD
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000502:physiology*; D002999:Clone Cells / Q000276:immunology; D003713:Dendritic Cells / Q000737:chemistry / Q000276:immunology*; D000078404:Epidermal Cells; D005260:Female; D005434:Flow Cytometry; D006433:Hemocyanins / Q000276:immunology; D007111:Immunity, Cellular / Q000528:radiation effects; D018799:Intercellular Adhesion Molecule-1; D007801:Langerhans Cells / Q000737:chemistry / Q000276:immunology*; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000032:analysis / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology*; D014466:Ultraviolet Rays
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin