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-2Rα 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 CD25high 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.

Retracted: CCR5 blockade in combination with rapamycin prolongs cardiac allograft survival in mice

“…+ cells in vivo [12][13][14]. Rapa (1 mg/ml) was purchased from Wyeth-Ayerst (Ayerst Laboratories, Pearl River, NY, USA) and diluted in saline for a dose of 0·1 mg/ml [15].…”

RETRACTED: Combined treatment with chemokine receptor 5 blocker and cyclosporine induces prolonged graft survival in a mouse model of cardiac transplantation

“…14 The anti-CD25 monoclonal Ab (rat immunoglobulin [Ig] G1, clone PC-61), which was purchased from Bioexpress Cell Culture Services (West Lebanon, NH) and is specific to interleukin [IL]-2R ␣-chain, causes depletion of CD25ϩ cells in vivo. [15][16][17] CsA was purchased from Novartis Pharma Schweiz AG, Bern, Switzerland.…”

γ-Tocopherol supplementation of allergic female mice augments development of CD11c+CD11b+dendritic cells in utero and allergic inflammation in neonates

“…In reports examining human maternal and paternal asthma associations with development of allergies in offspring, most associations are with maternal asthma (50). In animal studies, offspring of allergic mothers have increased responses to suboptimal doses of allergens (28,30,35,36,38,39,42). The sensitization to allergens and allergic responses are dependent on DCs, which produce regulatory cytokines (80,90).…”

“…Females were given the diets and mated with normal males. Three-day-old pups from five to six mothers per group were suboptimally sensitized by treating with only one 50-l intraperitoneal injection (rather than two injections) of 5 g OVA/1 mg alum (28,30,39). At 10, 11, and 12 days old, the pups were challenged for 15 min with 3% OVA (Fig.…”

“…In reports examining whether development of allergies in offspring associate with human maternal or paternal asthma, most associations are with maternal asthma (50). In animal studies, offspring from allergic mothers are predisposed to responses to suboptimal doses of allergens (28,30,35,36,38,39,42,50). Interestingly, in animal studies, dendritic cells (DCs), but not macrophages, from offspring of allergic mothers transfer the risk for allergies to naïve neonates (26).…”