title: Targeting of CD25 and glucocorticoid-induced TNF receptor family-related gene-expressing T cells differentially modulates asthma risk in offspring of asthmatic and normal mother mice.
abstract: Immunological mechanisms leading to increased asthma susceptibility in early life remain obscure. In this study, we examined the effects of neonatal Ab treatments targeting T cell populations on the development of an asthma syndrome. We used a model of increased asthma susceptibility where offspring of asthmatic BALB/c mother mice are more prone (than normal pups) to develop the disease. Neonatal pretreatment of naive pups with mAb directed against the IL-2Ralpha chain (CD25), the costimulatory molecule glucocorticoid-induced TNFR family related gene, and the inhibitory molecule CTLA-4 elicited contrasting effects in offspring depending on the mother's asthma status. Specifically, neonatal CD25(high) T cell depletion stimulated asthma susceptibility in normal offspring whereas it ameliorated the condition of pups born of asthmatic mothers. Conversely, glucocorticoid-induced TNFR family related gene ligation as a primary signal reduced the spleen cellularity and largely abrogated asthma susceptibility in asthma-prone offspring, without inducing disease in normal pups. Striking changes in Th1/Th2 cytokine levels, especially IL-4, followed mAb pretreatment and were consistent with the impact on asthma susceptibility. These results point to major differences in neonatal T cell population and responsiveness related to maternal asthma history. Interventions that temporarily remove and/or inactivate specific T cell subsets may therefore prove useful to attenuate early life asthma susceptibility and prevent the development of Th2-driven allergic airway disease.
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: Cedric
authors.initials: C
authors.lastname: Hubeau
authors.forename: Irina
authors.initials: I
authors.lastname: Apostolou
authors.forename: Lester
authors.initials: L
authors.lastname: Kobzik
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal / Q000009:adverse effects; D015703:Antigens, CD / Q000276:immunology*; D000943:Antigens, Differentiation / Q000276:immunology*; D001249:Asthma / Q000209:etiology* / Q000276:immunology; D060908:CTLA-4 Antigen; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D004198:Disease Susceptibility / Q000276:immunology; D053450:Glucocorticoid-Induced TNFR-Related Protein / Q000235:genetics / Q000276:immunology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009035:Mothers; D012306:Risk; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D016207:Cytokines; D053450:Glucocorticoid-Induced TNFR-Related Protein; D053645:Interleukin-2 Receptor alpha Subunit