The long-term objective of this project is to elucidate the mechanisms by which allergen sensitization and viral respiratory illnesses mutually influence one another early in life so as to confer risk for asthma. The relationships of asthma to wheezing lower respiratory illnesses (wLRIs) early in life and to sensitization to certain asthma-related allergens have often been addressed but remain poorly defined. This project proposes and tests a mechanistic basis for these relationships.
Three specific aims are proposed: 1) to identify the temporal patterns in and mechanisms of development of mitogen and RSV-specific T cytotoxic cell subsets (CD8+ Tc1 and Tc2) and mitogen and Alt-specific T helper cell subsets (CD4+ Th1 and Th2); 2) to determine the immune mechanisms for the absence of peripheral blood eosinopenic responses during viral respiratory infections in children at risk for asthma; and 3) to identify temporal pattern and the mechanisms of the induction of Alt-specific IgE and RSV-specific IgE in infancy in relation to the occurrence of LRIs and parental history of asthma. A unifying hypothesis is offered that children at risk for asthma may have wLRIs in the third year of life because of a persisting deficiency in cytotoxic function of the CD8+ Tc1 subset of cells, a deficiency which is suggested to originate differently in children with and without a parental history of asthma.
| Stern, D A; Lohman, I C; Wright, A L et al. (2004) Dynamic changes in sensitization to specific aeroallergens in children raised in a desert environment. Clin Exp Allergy 34:1563-669 |
| Guerra, Stefano; Carla Lohman, I; LeVan, Tricia D et al. (2004) The differential effect of genetic variation on soluble CD14 levels in human plasma and milk. Am J Reprod Immunol 52:204-11 |
| Guerra, Stefano; Lohman, I Carla; Halonen, Marilyn et al. (2004) Reduced interferon gamma production and soluble CD14 levels in early life predict recurrent wheezing by 1 year of age. Am J Respir Crit Care Med 169:70-6 |
| Krishnan, Subramaniam; Craven, Mary; Welliver, Robert C et al. (2003) Differences in participation of innate and adaptive immunity to respiratory syncytial virus in adults and neonates. J Infect Dis 188:433-9 |
| Brown, Mark A; Rad, Parmis Y; Halonen, Marilyn J (2003) Method of birth alters interferon-gamma and interleukin-12 production by cord blood mononuclear cells. Pediatr Allergy Immunol 14:106-11 |
