IL-2-IgG2b fusion protein suppresses murine contact hypersensitivity in vivo.
Interleukin-15 shares several functional properties with interleukin-2, and signals through the beta and gamma chain of the interleukin-2 receptor as well as through its own high affinity alpha chain. In agreement with the concept that interleukin-2 plays a key role in type IV immune responses, we have recently shown that an IL-2-IgG2b fusion protein potently suppresses Th1-type delayed type hypersensitivity reaction and Th2-type allergic sensitization in mice. We have now compared the in vivo effects of IL-2-IgG2b fusion protein with those of IL-15-IgG2b fusion protein in a murine model of Th1-type contact hypersensitivity reaction. Daily systemic injections of IL-2-IgG2b fusion protein during the sensitization phase or application of IL-2-IgG2b fusion protein just 2 h before and 10 h after antigen challenge significantly inhibited the contact hypersensitivity ear swelling response, and this without any overt signs of associated toxicity. Even local injection of IL-2-IgG2b fusion protein into the earlobe around the time of antigen challenge inhibited the ear swelling reaction significantly. In contrast, neither systemic nor local injection of the IL-15-IgG2b fusion protein modulated the contact hypersensitivity reaction significantly. IL-2-IgG2b but not IL-15-IgG2b fusion protein reduced migration of antigen-presenting cells from the skin to local lymph nodes, inhibited the expression of CD80 and CD86, and induced a significant higher number of CD4+CD25+ T cells. Therefore, the IL-2-IgGb fusion protein offers a powerful tool for suppressing and/or preventing T-cell-mediated hypersensitivity reaction in vivo.
Rückert
René
R
Department of Immunology and Cell Biology, Research Center Borstel, Borstel, Germany.
Brandt
Katja
K
Hofmann
Udo
U
Bulfone-Paus
Silvia
S
Paus
Ralf
R
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015704:CD4 Antigens / Q000032:analysis; D003713:Dendritic Cells / Q000187:drug effects / Q000502:physiology; D003877:Dermatitis, Contact / Q000517:prevention & control*; D005260:Female; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D019409:Interleukin-15 / Q000627:therapeutic use; D007376:Interleukin-2 / Q000627:therapeutic use*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D015375:Receptors, Interleukin-2 / Q000032:analysis; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology
D015704:CD4 Antigens; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D019409:Interleukin-15; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins