Hypothesis: Moderate-intensity aerobic exercise attenuates asthma pathogenesis through increased regulatory T (Treg) cell responses in vivo. Specific Aims: The aims that will test the hypothesis include: 1) determine the effects of moderate intensity aerobic exercise on Treg cell phenotype in a murine model of asthma; and 2) determine the effects of moderate intensity aerobic exercise on Treg cell function in a murine model of asthma. Experimental Approach: FoxpSEGFP reporter mice will be sensitized with ovalbumin (OVA) or control saline and exercised at a moderate intensity using a motorized treadmill; control mice will be permitted free movement within their cages. Upon completion of the OVA-sensitization and exercise protocol, CD4+ T cells will be isolated from spleen and lung tissues and examined for: 1) changes in FoxpS reporter (EGFP) expression; 2)Treg cell-related surface markers, including CD25, CD152 and membrane-bound TGFbeta; and 3) their effectiveness in suppressing T cell proliferation in vitro and asthma-related responses in vivo. Rationale: Asthma has increased in prevalence, morbidity and mortality over the past 20 years. Several clinical studies have reported that aerobic exercise improves cardiovascular fitness and the general quality of life for asthmatics; however, the effects of aerobic exercise on specific Treg cell-related responses, are not fully appreciated. Increasing evidence demonstrates that T lymphocytes, including CD4+CD25+Foxp3+ naturally occurring Treg (N-Treg) cells, play a central role in suppressing asthma pathogenesis. Specifically, the CD4+CD25+Foxp3+ N-Treg cell population has previously been shown to inhibit Th2 responses, airway eosinophilia and allergen-induced AHR. We present preliminary data that demonstrates that, in OVA-sensitized mice, moderate intensity aerobic exercise: 1) increases Treg cell responses; and 2) suppresses Th2 responses, airway eosinophilia and AHR. Relevance to Public Health and the NHLBI Mission: Proposed studies will test directly the effectiveness of aerobic exercise on the actions of regulatory T cells, a type of white blood cell, which suppress asthma disease severity and, thereby, improve lung health. [unreadable] [unreadable] [unreadable]