Allergic diseases, such as asthma, allergic rhinitis and eosinophilic gastroenteritis, are inflammatory diseases of the mucosa. After allergen exposure, IgE bearing cells, such as mast cells and basophils, are first activated. Later, T lymphocytes enter the mucosa, are activated by allergen and play a key role in regulating this inflammatory response through the elaboration of cytokines such as IL-4, IL-5 and IFN-gamma. This project seeks to examine the cytokine and mediator profiles of mast cell, basophil and T cell subpopulations that may be involved in the generation of inflammation in allergic diseases. ? ? We have extended our previous work with IgE receptor (FceRI) bearing dendritic cells and have identified a subset of CD2+ monocytes that express FceRI. These findings explain the contradictory previous studies that variably detected monocyte FceRI because its expression is limited to a small subset of CD2+ monocytes. FceRI expression by this subset correlated to serum IgE concentration and was reduced by therapeutic administration of anti-IgE during a clinical trial. These results identify a previously unrecognized subset of monocytes that express CD2 and FceRI and may play a role in allergic disease pathogenesis. This work establishes that FceRI is expressed by monocytes in an IgE dependent manner. These results further define the role of FceRI and IgE in antigen presentation, and suggest that via this mechanism, anti-IgE therapeutics may have an effect on allergen specific T cell activation.? ? Allergen specific T cells are memory CD4 T cells, which recently have been shown to consist of two subsets: CD45RO+, CCR7+ central memory and CD45RO+, CCR7- effector memory T cells. We have previously investigated (Elson, 1995) a third marker of memory T cells, CD27, which is lost on highly differentiated memory T cells. In collaboration with Dr. Peter Lipsky, we examined the expression of CC27 and CCR7 on memory T cells in patients with Systemic Lupus Erythematosis (SLE), Rheumatoid Arthritis, and Allergic Asthma. T cells from patients with SLE were unique for having increased numbers of highly differentiated memory T cells (CD45RO+, CCR7-, CD27-) relative to healthy controls and the other diseases populations noted. These results demonsate that in SLE there is a wholesale shift in T cell differentiation towards terminally differentiated memory subsets, whereas in allergic asthma, these changes may be limited to the allergen specific T cell population. ? ? In collaboration with Dr. Helene Rosenberg we have examined T cell and natural killer (NK) cell cytokine responses to pneumovirus infection in a mouse model. Using these techniques we can identify the cellular source of IFN-gamma expression in both bronchoalveolar lavage and lung tissue. We have examined these responses in both uninfected and infected mice, using several eosinophil deleted mouse strains. These results demonstrate that pneumovirus infection is associated with increased trafficking of T and NK cells to the lung. During viral infection, the number of NK cells able to express IFN-gamma increases dramatically. These results demonstrate how both acquired and innate immune responses to viruses synergize to promote immunity.
| Liu, Rebecca Berlant; Engels, Boris; Schreiber, Karin et al. (2013) IL-15 in tumor microenvironment causes rejection of large established tumors by T cells in a noncognate T cell receptor-dependent manner. Proc Natl Acad Sci U S A 110:8158-63 |
| Liu, Rebecca B; Engels, Boris; Arina, Ainhoa et al. (2012) Densely granulated murine NK cells eradicate large solid tumors. Cancer Res 72:1964-74 |
| Prussin, Calman; Metcalfe, Dean D (2006) 5. IgE, mast cells, basophils, and eosinophils. J Allergy Clin Immunol 117:S450-6 |
| Fritsch, Ruth D; Shen, Xinglei; Illei, Gabor G et al. (2006) Abnormal differentiation of memory T cells in systemic lupus erythematosus. Arthritis Rheum 54:2184-97 |
| Garvey, Tara L; Dyer, Kimberly D; Ellis, John A et al. (2005) Inflammatory responses to pneumovirus infection in IFN-alpha beta R gene-deleted mice. J Immunol 175:4735-44 |
| Foroughi, Shabnam; Prussin, Calman (2005) Clinical management of eosinophilic gastrointestinal disorders. Curr Allergy Asthma Rep 5:259-61 |
| Prussin, Calman; Metcalfe, Dean D (2003) 4. IgE, mast cells, basophils, and eosinophils. J Allergy Clin Immunol 111:S486-94 |
| Prussin, Calman; Griffith, Daniel T; Boesel, Kevin M et al. (2003) Omalizumab treatment downregulates dendritic cell FcepsilonRI expression. J Allergy Clin Immunol 112:1147-54 |
| Foster, Barbara; Metcalfe, Dean D; Prussin, Calman (2003) Human dendritic cell 1 and dendritic cell 2 subsets express FcepsilonRI: correlation with serum IgE and allergic asthma. J Allergy Clin Immunol 112:1132-8 |
| Metcalfe, Dean D (2003) Introduction: what are the issues in addressing the allergenic potential of genetically modified foods? Environ Health Perspect 111:1110-3 |
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