This laboratory studies the role of the skin as an immunological organ. We study the mechanisms involved in allergic contact dermatitis and use this knowledge to better understand lymphocyte- mediated skin diseases. In the past two years we have focussed our studies on using the immunological elements of the epidermis (and dermis) and to develop cell lines in order to induce and/or modulate certain types of immunological reactions. We are using four different approaches- 1)sensitization via intradermal injection of naked DNA; 2) development of cell lines that can become potent antigen-presenting cells in vitro and in vivo; 3)investigation of bone-marrow derived dendritic cells to determine their potential for in vivo and in vitro manipulation and 4) development of a model of immune deviation that will facilitate the modulation of Th1 and Th2 responses. We have recently found that in vivo intradermal injection of DNA encoding certain proteins induces potent sensitization. The DNA is picked up by Langerhans cells, transcribed, and is presented as protein to T cells in the regional lymph nodes. These studies are currently taking advantage of recently generated dendritic cell lines such as XS52 and XS106 which we are attempting to transfect with various DNA constructs that encode for different proteins. These dendritic cells as well as others that we are currently developing from bone marrow aspirates are being cultured in various cytokine- and growth factor-containing media in order to modulate their phenotypic and functional characteristics. To date, we have found that IL-4 and anti CD40 mAb can cause increased expression of Class II MHC molecules as well as costimulatory molecules and can cause enhanced antigen presenting capacity of the cells. We have also found that bone-marrow derived dendritic cells cannot induce potent antigen-specific T cell responses to protein antigens but, when modified with haptens such as TNCB in vitro and injected in vivo, can induce hapten-specific MHC-restricte contact sensitivity. We have also developed ELISA assays fo cytokines to determine the type of immunological response that ensues when different types of antigens, cells and/or adjuvants are used for sensitization. In this regard, we are attempting to develop a model whereby Th2 responses predominate and prevent certain types of Th1 responses to occur or potentially even reverse the Th1 responses. This form of immune deviation may be very valuable in modulating the deleterious Th1 responses that occur in certain infectious and autoimmune diseases. - Langerhans cells, vaccines, dendritic cells, contact sensitivity, - Human Subjects
| Miyagawa, Fumi; Tagaya, Yutaka; Kim, Brian S et al. (2008) IL-15 serves as a costimulator in determining the activity of autoreactive CD8 T cells in an experimental mouse model of graft-versus-host-like disease. J Immunol 181:1109-19 |
| Takeuchi, Satoshi; Katz, Stephen I (2006) Use of interleukin 7 receptor-alpha knockout donor cells demonstrates the lymphoid independence of dendritic cells. Blood 107:184-6 |
