Research Interests

Robert Tigelaar, Ph.D.'s research focuses on dendritic epidermal T cells (DETC), cells which populate the skin of all normal strains of mice and express homogeneous Vgamma5/Vdelta1 TCRs lacking junctional (CDR3 region) diversity. Use of different strains of TCR delta-/- mice and selective reconstitution of such mice via adoptive transfer has recently shown that Vgamma5+ DETC, but not other gamma delta cells, down-regulate a variety of cutaneous inflammatory responses, including a spontaneous, localized, genetically-dependent, TCR alpha beta+ T cell-dependent, and environmentally-dependent, chronic dermatitis that shares several features of human atopic dermatitis. Current collaborative studies with Dr. Adrian Hayday (Guy's Hospital, London) include:

1. Characterizing the genes expressed by "resting" and "activated" DETC by serial analysis of gene expression (SAGE) and comparing such expression patterns with other IEL and recirculating T cell subsets.
2. Investigating selected candidate DETC anti-inflammatory cytokines/effector molecules by reconstituting TCR delta-/- recipients with DETC precursors rendered deficient (via gene "knockout" or siRNA "knock-down") in candidate anti-inflammatory molecules.
3. Utilizing genome-wide microsatellite mapping, to identify the genetic interval(s), and ultimately the specific genes, controlling susceptibility/resistance to the spontaneous dermatitis that develops in some, but not other TCR delta -/- mice.
4. Utilizing cellular, molecular and genetic studies to identify the physiologic ligands for TCR gamma/delta+ T cells that trigger both their positive selection in the thymus and their activation in peripheral epithelial tissues such as the skin and GI tract.