Chemokines are a family of over 30 small secreted proteins whose best described function is chemoattraction. Chemokines receptors, of which 19 are described, are seven-transmembrane domain linked G-protein coupled proteins. Since chemokines mediate migration towards (and within) secondary lymphoid tissue and inflamed peripheral sites, the history and function of a T cell determines which chemokine recptors it may express. Thus, any attempt to comprehensively define T cell function must include characterization of chemokine receptor expression. My laboratory uses chemokine receptor expression in addition to cytokine secretion profiles to define T cell functional responses to the following pathological and molecular stimuli: 1. Respiratory Syncycial Virus (RSV) Almost all children have been infected with RSV by the age of 2 years, some more than once. RSV infection is the most common event that precipitates wheezing in children and response to RSV in infancy strongly predicts the presence of childhood asthma. Thus, characterizing the T cell response to RSV may provide insight towards understanding childhood asthma. To that end, there are two experimental projects planned--defining the T cell responses to RSV and other respiratory viruses by tonsil T cells, and determining the effect of chemokines as adjuvants in mouse models of RSV pneumonitis. 2. Survival cytokines While the effect of stimulation in context of polarizing cytokines on chemokine receptor expression and function has been amply studied, it is unknown how survival cytokines affect T cell function and chemokine receptor expression. 3. Multidrug Resistance Proteins Members of the MDR and MRP families of proteins are expressed on T cells, and may affect T cell function. Since there are many molecules that may be used to modulate MDR activity, the MDR and MRP proteins may be a novel target for therapy of asthma and allergy.
