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T Cells in the Lungs and Their Regulatory Roles in Th1 Response and Host Defense against Pulmonary Infection with Cryptococcus neoformans1
* Department of Internal Medicine, Division of Infectious Diseases, Graduate School and Faculty of Medicine, University of the Ryukyus, Okinawa, Japan; and
Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan
The present study was designed to elucidate the role of 
T cells in the host defense against pulmonary infection with Cryptococcus neoformans. The T cells in lungs commenced to increase on day 1, reached a peak level on day 3 or 6, and then decreased on day 10 after intratracheal infection. The increase of these cells was similar in monocyte chemoattractant protein (MCP)-1-deficient mice, although that of NK and NKT cells was significantly reduced. The number of live microorganisms in lungs on days 14 and 21 was significantly reduced in mice depleted of T cells by a specific mAb compared with mice treated with control IgG. Similarly, elimination of this fungal pathogen was promoted in T cell-deficient (TCR-–/–) mice compared with control littermate mice. Finally, lung and serum levels of IFN- on days 7 and 14 and on day 7 postinfection, respectively, were significantly higher in TCR-–/– mice than in littermate mice, whereas levels of TGF-
showed the opposite results. IL-4 and IL-10 were not different between these mice. IFN- production by draining lymph node cells upon restimulation with cryptococcal Ags was significantly higher in the infected TCR-–/– mice than in control mice. Our results demonstrated that T cells accumulated in the lungs in a manner different from NK and NKT cells after cryptococcal infection and played a down-modulatory role in the development of Th1 response and host resistance against this fungal pathogen.
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