This project proposes to investigate the interactions between T lymphocytes in the context of chronic inflammation and infection. The hypothesis is that B. burgdorferi infection activates the vascular endothelium, enhancing extravasation of T lymphocytes that secret type 1 proinflammatory cytokines. To test this central hypothesis, the PI will use in vitro models to pursue the following specific aims: 1) Determine the subpopulations of T lymphocytes that migrate across endothelium exposed to B. burgdorferi; 2) Identify the adhesion molecules and chemo-attractants involved in the migration of T lymphocytes across spirochete-stimulated endothelium; and 3) Explore the capacity of the host cytokine, interleukin (IL)10, to modulate interactions of T lymphocytes with endothelium activated by B. burgdorferi. These studies will provide greater insight into how accumulation of T lymphocytes is regulated not only in Lyme disease, but also in chronic inflammation in general.
| Dame, Tarah M; Orenzoff, Barbara L; Palmer, Lance E et al. (2007) IFN-gamma alters the response of Borrelia burgdorferi-activated endothelium to favor chronic inflammation. J Immunol 178:1172-9 |
| Gergel, Edna I; Furie, Martha B (2004) Populations of human T lymphocytes that traverse the vascular endothelium stimulated by Borrelia burgdorferi are enriched with cells that secrete gamma interferon. Infect Immun 72:1530-6 |
| Lisinski, Tracy J; Furie, Martha B (2002) Interleukin-10 inhibits proinflammatory activation of endothelium in response to Borrelia burgdorferi or lipopolysaccharide but not interleukin-1beta or tumor necrosis factor alpha. J Leukoc Biol 72:503-11 |
