Rapid on/off cycling of cytokine production by virus-specific CD8+ T cells

被引:216
作者
Slifka, MK [1 ]
Rodriguez, F [1 ]
Whitton, JL [1 ]
机构
[1] Scripps Res Inst, Dept Neuropharmacol, La Jolla, CA 92037 USA
关键词
D O I
10.1038/43454
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
CD8-positive T cells protect the body against viral pathogens by two important mechanisms: production of antiviral cytokines(1,2) and lysis of infected cells(3,4). Cytokine production can have both local and systemic consequences(5,6), whereas cytolytic activity is limited to infected cells that are in direct contact with T cells(7-9). Here we analyse activated CD8-positive T cells from mice infected with lymphocytic choriomeningitis virus and find that cytokines are not produced ex vivo in the absence of peptide stimulation, but that they are rapidly generated after T cells encounter viral peptides bound to the major histocompatibility complex. Remarkably, cytokine production ceases immediately upon dissociation of the T cells from their targets and resumes when antigenic contact is restored. In contrast to the 'on/off/on' cycling of cytokines, the pore-forming cytotoxic protein perforin is constitutively maintained. Our results indicate that there is differential expression of effector molecules according to whether the antiviral product is secreted (like cytokines) or stored inside the cell (like perforin). The ability to turn cytokines on and off while maintaining intracellular stores of perforin shows the versatility of the cellular immune response and provides a mechanism for maintaining effective immune surveillance while reducing systemic immunopathology.
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页码:76 / 79
页数:4
相关论文
共 26 条
[1]   SELECTION OF GENETIC-VARIANTS OF LYMPHOCYTIC CHORIOMENINGITIS VIRUS IN SPLEENS OF PERSISTENTLY INFECTED MICE - ROLE IN SUPPRESSION OF CYTO-TOXIC LYMPHOCYTE-T RESPONSE AND VIRAL PERSISTENCE [J].
AHMED, R ;
SALMI, A ;
BUTLER, LD ;
CHILLER, JM ;
OLDSTONE, MBA .
JOURNAL OF EXPERIMENTAL MEDICINE, 1984, 160 (02) :521-540
[2]   Degranulation plays an essential part in regulating cell surface expression of Fas ligand in T cells and natural killer cells [J].
Bossi, G ;
Griffiths, GM .
NATURE MEDICINE, 1999, 5 (01) :90-96
[3]   Massive expansion of antigen-specific CD8+ T cells during an acute virus infection [J].
Butz, EA ;
Bevan, MJ .
IMMUNITY, 1998, 8 (02) :167-175
[4]   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
[5]   NEUROPATHOGENIC ACTIONS OF CYTOKINES ASSESSED IN TRANSGENIC MICE [J].
CAMPBELL, IL .
INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE, 1995, 13 (3-4) :275-284
[6]   Virus-specific CD8+ T cells in primary and secondary influenza pneumonia [J].
Flynn, KJ ;
Belz, GT ;
Altman, JD ;
Ahmed, R ;
Woodland, DL ;
Doherty, PC .
IMMUNITY, 1998, 8 (06) :683-691
[7]   To kill or to cure: Options in host defense against viral infection [J].
Guidotti, LG ;
Chisari, FV .
CURRENT OPINION IN IMMUNOLOGY, 1996, 8 (04) :478-483
[8]   ANTIGEN PRESENTATION AND CYTOTOXIC T-LYMPHOCYTE KILLING STUDIED IN INDIVIDUAL, LIVING CELLS [J].
HAHN, K ;
DEBIASIO, R ;
TISHON, A ;
LEWICKI, H ;
GAIRIN, JE ;
LAROCCA, G ;
TAYLOR, DL ;
OLDSTONE, M .
VIROLOGY, 1994, 201 (02) :330-340
[9]   Local and systemic cytokine responses during experimental human influenza A virus infection - Relation to symptom formation and host defense [J].
Hayden, FG ;
Fritz, RS ;
Lobo, MC ;
Alvord, WG ;
Strober, W ;
Straus, SE .
JOURNAL OF CLINICAL INVESTIGATION, 1998, 101 (03) :643-649
[10]   CYTOTOXICITY MEDIATED BY T-CELLS AND NATURAL-KILLER-CELLS IS GREATLY IMPAIRED IN PERFORIN DEFICIENT MICE [J].
KAGI, D ;
LEDERMANN, B ;
BURKI, K ;
SEILER, P ;
ODERMATT, B ;
OLSEN, KJ ;
PODACK, ER ;
ZINKERNAGEL, RM ;
HENGARTNER, H .
NATURE, 1994, 369 (6475) :31-37