IMMUNE-RESPONSE AGAINST LYMPHOCYTIC CHORIOMENINGITIS VIRUS-INFECTION IN MICE WITHOUT CD8-EXPRESSION

被引:176
作者
FUNGLEUNG, WP
KUNDIG, TM
ZINKERNAGEL, RM
MAK, TW
机构
[1] UNIV TORONTO, ONTARIO CANC INST, 500 SHERBOURNE ST, TORONTO M4X 1K9, ONTARIO, CANADA
[2] UNIV TORONTO, DEPT MED BIOPHYS & IMMUNOL, TORONTO M4X 1K9, ONTARIO, CANADA
[3] UNIV ZURICH, INST PATHOL, CH-8006 ZURICH, SWITZERLAND
关键词
D O I
10.1084/jem.174.6.1425
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The immune response against lymphocytic choriomeningitis virus (LCMV) was studied in a mutant mouse strain that does not possess CD8+ T lymphocytes. Virus-specific cytotoxic T cell activity was generated in spleens of wild-type mice in an acute LCMV infection but was not measurable in mutant mice. Injection of replicating LCMV into footpads of wild-type mice induced a CD8+ T cell-mediated swelling that peaked on day 8, followed by a CD4+ T cell-mediated swelling that peaked on day 11, whereas mutant mice exhibited only the CD4+ T cell-mediated swelling. After intracerebral inoculation with LCMV-Armstrong, all wild-type mice died of classical CD8+ T cell-dependent choriomeningitis in 8-10 days. Mutant mice showed symptoms of general malaise but most of them survived. Mutant mice depleted of CD4+ T cells by monoclonal antibody treatment showed no clinical signs of sickness. On day 9 after intravenous infection with LCMV-WE, virus was detected at high titers in spleens and livers of mutant mice but not in those of wild-type mice. On day 70 after injection of LCMV-WE into footpads, virus was not detected in wild-type mice and in one of the three mutant mice tested, but was still measurable in kidneys of the other two mutant mice. These results confirm in a new animal model that CD8+ T cell-mediated immunity is crucial in LCMV clearance and in the immunopathological disease during LCMV infection. In addition, our results demonstrated a less severe form of choriomeningitis mediated by CD4+ T cells and slow clearance of LCMV by alternative pathways independent of CD8+ T cells.
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页码:1425 / 1429
页数:5
相关论文
共 28 条
[1]   MECHANISM OF RECOVERY FROM ACUTE VIRUS-INFECTION .3. SUBCLASS OF LYMPHOCYTE-T MEDIATING CLEARANCE OF LYMPHOCYTIC CHORIOMENINGITIS VIRUS FROM THE SPLEENS OF MICE [J].
ASSMANNWISCHER, U ;
SIMON, MM ;
LEHMANNGRUBE, F .
MEDICAL MICROBIOLOGY AND IMMUNOLOGY, 1985, 174 (05) :249-256
[2]   INDUCTION OR PREVENTION OF IMMUNOPATHOLOGICAL DISEASE BY CLONED CYTOTOXIC T-CELL LINES SPECIFIC FOR LYMPHOCYTIC CHORIOMENINGITIS VIRUS [J].
BAENZIGER, J ;
HENGARTNER, H ;
ZINKERNAGEL, RM ;
COLE, GA .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1986, 16 (04) :387-393
[3]  
BINDER D, 1991, IN PRESS J IMMUNOL
[4]  
Buchmeier M J, 1980, Adv Immunol, V30, P275, DOI 10.1016/S0065-2776(08)60197-2
[5]   BIOLOGY OF CLONED CYTO-TOXIC LYMPHOCYTES-T SPECIFIC FOR LYMPHOCYTIC CHORIOMENINGITIS VIRUS - CLEARANCE OF VIRUS INVIVO [J].
BYRNE, JA ;
OLDSTONE, MBA .
JOURNAL OF VIROLOGY, 1984, 51 (03) :682-686
[6]   THERAPY WITH MONOCLONAL-ANTIBODIES BY ELIMINATION OF T-CELL SUBSETS INVIVO [J].
COBBOLD, SP ;
JAYASURIYA, A ;
NASH, A ;
PROSPERO, TD ;
WALDMANN, H .
NATURE, 1984, 312 (5994) :548-551
[7]  
COLE GA, 1972, NATURE, V238, P335, DOI 10.1038/238335a0
[8]  
DOHERTY PC, 1974, TRANSPLANT REV-DENMA, V19, P89
[9]   CD8 IS NEEDED FOR DEVELOPMENT OF CYTOTOXIC T-CELLS BUT NOT HELPER T-CELLS [J].
FUNGLEUNG, WP ;
SCHILHAM, MW ;
RAHEMTULLA, A ;
KUNDIG, TM ;
VOLLENWEIDER, M ;
POTTER, J ;
VANEWIJK, W ;
MAK, TW .
CELL, 1991, 65 (03) :443-449
[10]  
HAUSER T, 1990, MED MICROBIOL IMMUN, V179, P95