Pretreatment With Inactivated Bacillus C almette– G uerin Increases CD 4+ CD 25+ Regulatory T Cell Function and Decreases Functional and Structural Effects of Asthma Induction in a Rat Asthma Model

Bacillus C almette– G uerin ( BCG ) has been shown to have therapeutic effects on asthma through CD 4+ CD 25+ regulatory T cells ( T regs). We sought to assess pretreatment with inactivated BCG on CD 4+ CD 25+ T regs and its functional and structural effects in rat asthma model. The rat asthma model was established using ovalbumin ( OVA ) sensitization and challenge. Ten rats were pretreated with BCG prior to OVA and received continued BCG injections during OVA challenge ( BCG + OVA group), 10 rats were treated with OVA alone ( OVA group), and 10 rats were treated with saline (control group). After 9 weeks, histamine dihydrochloride effect on airway resistance was measured. Number of CD 4+ CD 25+ T regs was measured by flow cytometry, expression of F oxp3 and CTLA ‐4 mRNA was measured, and serum TGF ‐β levels were determined. Differential cell count in bronchoalveolar lavage fluid ( BALF ) was determined, and lung tissue was processed and stained with hematoxylin and eosin, M asson's trichrome, and alcine blue and periodic acid S chiff's reaction to evaluate inflammatory cell infiltration, collagen deposition, and presence of goblet cells, respectively. BCG treatment led to an increase in CD 4+ CD 25+ T regs, as well as an increase in F oxp3 and CTLA ‐4 expression and serum TGF ‐β levels. In addition, we observed a decrease in histamine dihydrochloride–induced airway resistance, a decrease in inflammatory leukocytes in BALF , and a decrease in airway remodeling indicators in BCG + OVA ‐treated rats compared with OVA ‐treated rats. Intradermally injected inactivated BCG has the potential to improve airway inflammation, airway resistance, and airway remodeling through a mechanism that may involve CD 4+ CD 25+ T regs.