Jpn. J. Infect. Dis., 57, 137-145, 2004
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Invited Review
Regulation by Innate Immune T Lymphocytes in the Host Defense against Pulmonary Infection with Cryptococcus neoformans
Kazuyoshi Kawakami*
Division of Infectious Diseases, Department of Internal Medicine, Graduate School and Faculty of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan
(Received February 26, 2004)
*Corresponding author: Mailing address: Division of Infectious Diseases, Department of Internal Medicine, Graduate School and Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215, Japan. Tel: +81-98-895-1144, Fax: +81-98-895-1414, E-mail: kawakami@med.u-ryukyu.ac.jp
This article is an Invited Review based on a lecture presented at the 13th Symposium of the National Institute of Infectious Diseases, Tokyo, 21 May 2003.
CONTENTS:
1. Introduction
2. Basics in the host defense to cryptococcal infection
3. Role of NKT cells
3-1. General features of NKT cells
3-2. Regulatory role of NKT cells in Th1-Th2 cytokine balance
3-3. Significance of NKT cells in infectious diseases
3-4. Recruitment of NKT cells in the lung after cryptococcal infection
3-5. Role of NKT cells in Th1 response and host defense to cryptococcal
infection
3-6. Natural ligands
3-7. Induction of Th1 response and host defense to cryptococcal
infection by ligand-specific activation
4. Role of gd T cells
4-1. General features of gd T cells
4-2. Natural ligands
4-3. Significance of gd T cells in
infectious diseases
4-4. Regulatory role in host defense to cryptococcal infection
5. Conclusions
SUMMARY: Recently, innate immune lymphocytes, such as natural killer (NK) T cells and gd antigen receptor-bearing T (gd T) cells, have garnered much attention, and their biological significance in the tumor immunity, allergic diseases and infectious diseases is extensively exploited. We have addressed the role of these cells in the host defense using a mouse model of pulmonary infection with Cryptococcus neoformans, which frequently causes fatal meningoencephalitis in AIDS patients. Host defense to this fungal pathogen is largely mediated by cellular immunity, and type-1 helper T (Th1) cells play a central role in this process. This infection causes a prompt accumulation of both NKT and gd T cells in the lung tissues in a monocyte chemoattractant protein (MCP)-1-dependent or -independent manner, respectively. Genetic deletion of Va14+ NKT cells ameliorates the Th1 response and clearance of microorganisms in the lungs, whereas these host protective responses are rather enhanced in mice lacking gd T cells. Thus, in some aspect, these innate immune lymphocytes may co-regulate the Th1-mediated response for induction of the moderate host defense. gd T cells may act to keep the balance of Th1-Th2 responses in a proper manner by suppressing the exaggerated Th1 response caused by NKT cells. In this review, I describe the recent research development in the innate immune host defense against cryptococcal infection in respiratory organs with emphasis on our data in the regulatory role of NKT cells and gd T cells.