Véronique Schulten1, April Frazier1, Agustin Calatroni2, Meyer Kattan3, Leonard B Bacharier4, George T O'Connor5, Megan T Sandel6, Robert A Wood7, Lisa M Wheatley8, Alkis Togias8, Cynthia M Visness2, Amy Dresen9, James E Gern9, Alessandro Sette1,10. 1. La Jolla Institute for Immunology, La Jolla, California. 2. Rho, Inc, Chapel Hill, North Carolina. 3. Department of Pediatrics, Columbia University, New York, New York. 4. Department of Pediatrics, Washington University School of Medicine, St Louis, Missouri. 5. Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts. 6. Department of Pediatrics, Boston Medical Center and Boston University School of Medicine, Boston, Massachusetts. 7. Department of Pediatrics, John Hopkins University Medical Center, Baltimore, Maryland. 8. National Institute of Allergy, Infectious Diseases, Bethesda, Maryland. 9. Department of Pediatrics, University of Wisconsin, Madison, Wisconsin. 10. Department of Medicine, University of California San Diego, La Jolla, California.
Abstract
BACKGROUND: Allergy to German cockroach (CR) is common in urban environments and is an important allergen in children with asthma. OBJECTIVE: We hypothesize that the evolution of allergic sensitization and clinical disease is associated with distinct patterns of allergen-specific T cell reactivity. To test this hypothesis, a subset of high-risk inner-city children participating in the URECA (Urban Environment and Childhood Asthma) birth cohort were selected to evaluate CR-specific T cell reactivity from three distinct groups based on acquisition of aeroallergen sensitivity from ages 2 to 10: low atopy with minimal to no sensitivity (n = 26), early-onset allergic sensitization (n = 25) and late-onset allergic sensitization (n = 25). METHODS: Using pools of previously identified CR-derived T cell epitopes, we characterized the allergen-specific T cell response in these 76 subjects from blood samples obtained at age 10. CR-specific production of IL-5, IFNγ and IL-10 was measured by ELISPOT following two-week in vitro culture with CR extract. RESULTS: T cell responses were significantly higher in the early-onset atopy group compared to low atopy (P = 0.01), and a trend for higher cytokine production in the late onset compared to the low atopy cohort was also observed (P = 0.06). T cell responses were similar between early- and late-onset cohorts. Furthermore, a comparison of T cell reactivity between asthmatic and non-asthmatic individuals revealed significantly higher cytokine production in asthmatics compared to non-asthmatics (P = 0.02) within both the CR-allergic and non-allergic cohorts. CONCLUSIONS AND CLINICAL RELEVANCE: In conclusion, the present study reports that higher T cell reactivity is associated with allergen sensitization and asthma. Interestingly, no significant difference in T cell reactivity was observed in allergic children with early-onset versus late-onset atopy.
BACKGROUND:Allergy to German cockroach (CR) is common in urban environments and is an important allergen in children with asthma. OBJECTIVE: We hypothesize that the evolution of allergic sensitization and clinical disease is associated with distinct patterns of allergen-specific T cell reactivity. To test this hypothesis, a subset of high-risk inner-city children participating in the URECA (Urban Environment and Childhood Asthma) birth cohort were selected to evaluate CR-specific T cell reactivity from three distinct groups based on acquisition of aeroallergen sensitivity from ages 2 to 10: low atopy with minimal to no sensitivity (n = 26), early-onset allergic sensitization (n = 25) and late-onset allergic sensitization (n = 25). METHODS: Using pools of previously identified CR-derived T cell epitopes, we characterized the allergen-specific T cell response in these 76 subjects from blood samples obtained at age 10. CR-specific production of IL-5, IFNγ and IL-10 was measured by ELISPOT following two-week in vitro culture with CR extract. RESULTS: T cell responses were significantly higher in the early-onset atopy group compared to low atopy (P = 0.01), and a trend for higher cytokine production in the late onset compared to the low atopy cohort was also observed (P = 0.06). T cell responses were similar between early- and late-onset cohorts. Furthermore, a comparison of T cell reactivity between asthmatic and non-asthmatic individuals revealed significantly higher cytokine production in asthmatics compared to non-asthmatics (P = 0.02) within both the CR-allergic and non-allergic cohorts. CONCLUSIONS AND CLINICAL RELEVANCE: In conclusion, the present study reports that higher T cell reactivity is associated with allergen sensitization and asthma. Interestingly, no significant difference in T cell reactivity was observed in allergicchildren with early-onset versus late-onset atopy.
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