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In another study of the immunosuppressive effects of exposure to cigarette smoke in female F-344 rats, chronic, daily whole-body exposures of up to 30 months to mainstream smoke from 1R3 reference cigarettes (two-second puff, two puffs per minute, 70-mL puff) reduced proliferation mediated by T-cell antigen and led to constitutive activation of enzymes involved in activation of the T-cell antigen receptor, tyrosine phosphorylase, and phospholipase C-1 (Kalra et al