Delayed production of TNF-α in neonatal mice in response to Pneumocystis carinii infection corresponds to increased TGF-β levels in the lungs (51.11)

Abstract

Abstract Neonatal mice challenged with Pneumocystis carinii (PC) exhibit a three week delay in clearance as compared to adults, corresponding to a delayed CD4+ T cell infiltration into the alveolar spaces. We have published that messenger RNA levels of transforming growth factor (TGF)-β and interleukin (IL)-10 are constitutively expressed in neonatal lungs, suggesting that the lung environment is not adequate to recruit circulating lymphocytes. We have since found that pups have increased TGF-β1 protein levels compared to adults until three weeks of age. The infiltration of CD4+ T cells corresponded to decreasing lung TGF-β levels. Moreover, production of TNF–α by CD4+ T cells was also delayed in pups compared to adults. Ongoing experiments will determine whether TGF-β dampens the proinflammatory response until it is developmentally downregulated or if decreased TGF-β levels follow lung infiltration by activated CD4+ T cells. This research was supported by PHS grant HL062053.