Laura Bursch

E-mail: acker018@umn.edu

Thesis Advisor: Kris Hogquist

Year entered: 2003

Degrees received:
B.S., Biomedical Science, Western Michigan University, Kalamazoo, Michigan, 2001

Honors and Awards:

• 3M Graduate Fellowship, 2003-2007
• MICaB Travel Award- Fall 2005
• Golden Pipetman Award- Fall 2006

Thesis research:
Dendritic cells are the primary antigen presenting cells responsible for inducing T cell mediated immune responses and maintaining T cell tolerance to self antigens. Langerhans cells (LC) are a subset of specialized dendritic cells that reside within the barrier surfaces, including the epidermis of the skin.  In the steady state, LC traffic to the skin draining lymph nodes carrying antigens from the epidermis.  LC are unique among hematopoietic cells in that they are radioresistant within the epidermis and can be renewed from local precursors within the skin.  Thus, in hematopoietic chimeras, LC remain of host origin for up to one year following lethal irradiation.  In order to study the radioresistance of LC and other dendritic cell populations, we created hematopoietic chimeras using mice in which EGFP was knocked-in to the Langerin locus.  As expected, epidermal EGFP+ LC were host derived.  However, we discovered a prominent population off EGFP+ in the dermis, which were predominantly donor derived.  In fact, such donor derived LC migrated from TRITC painted skin, and comprised the majority of LC in skin draining lymph nodes.  In addition, differential expression of CD11b and Ep-CAM by donor and host derived LC suggests that these populations actually represent distinct subsets.  Furthermore, following ablation of LC in mice in which EGFP was fused to the diphtheria toxin receptor, LC with low expression of CD11b return to the dermis and skin draining lymph nodes well before epidermal LC were detected.  The presence of two distinct populations of LC may provide insight into the differential results obtained in varying LC depletion systems when addressing the role of LC in contact hypersensitivity (CHS) responses.  We will address the functional properties of these dermal Langerhans cells in both CHS responses and induction of antigen specific T cell immune responses to epicutaneously applied antigens.  We have identified a novel population of LC which is radiosensitive and resides in the dermis.  This finding will be integral to better understanding of immune responses within the skin.

Publications:

Mayerova, D.,  E.A. Parke, L.S. Bursch, O.A. Odumade, K.A. Hogquist.  2004.  Langerhans cells activate naive self-antigen-specific CD8 T cells in the steady state.  Immunity.  21(3):391-400.

Mayerova, D., L. Wang, L.S. Bursch, K.A. Hogquist.  2006.  Conditioning of Langerhans cells induced by a primary CD8 T cell response to self-antigen in vivo.  J Immunol.  176(8):4658-65.

Stoitzner, P., C.H. Tripp, A. Eberhart, K.M. Price, J.Y. Jung, L. Bursch, F. Ronchese, N. Romani.  2006.  Langerhans cells cross-present antigen derived from skin.  Proc Natl Acad Sci U S A.  103(20):7783-8.