Impaired gamma interferon responses against parvovirus B19 by recently infected children

被引:39
作者
Corcoran, A
Doyle, S
Waldron, D
Nicholson, A
Mahon, BP [1 ]
机构
[1] Natl Univ Ireland, Mucosal Immunol Lab, Dept Biol, Maynooth, Kildare, Ireland
[2] Natl Univ Ireland, Biotechnol Lab, Maynooth, Kildare, Ireland
[3] Our Lady Lourdes Hosp, Drogheda, County Louth, Ireland
关键词
D O I
10.1128/JVI.74.21.9903-9910.2000
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Parvovirus B19 is the causative agent of "fifth disease" of childhood. It has been implicated in a variety of conditions, including unsuccessful pregnancy and rheumatoid arthritis, and is a potential contaminant of blood products, There has been little study of immunity to parvovirus B19, and the exact nature of the protective humoral and cell-mediated immune response is unclear. Immune responses to purified virus capsid proteins, VP1 and VP2, were examined from a cohort of recently infected children and compared with responses from long-term convalescent volunteers. The results demonstrate that antibody reactivity is primarily maintained against conformational epitopes in VP1 and VP2. The unique region of VPI appears to be a major target for cell-mediated immune responses, particularly in recently infected individuals. We confirm that antibody reactivity against linear epitopes of VP2 is lost shortly after infection but find no evidence of the proposed phenotypic switch in either the subclass of parvovirus B19-specific antibody or the pattern of cytokine production by antigen-specific T cells. The dominant subclass of specific antibody detected from both children and adults was immunoglobulin G1. No evidence was found for interleukin 4 (IL-4) or IL-5 production by isolated lymphocytes from children or adults, In contrast, lymphocytes from convalescent adults produced a typical type 1 response associated with high levels of IL-2 and gamma interferon (IFN-gamma). However, we observed a significant (P < 0.001) deficit in the production of IFN-gamma in response to VP1 or VP2 from lymphocytes isolated from children. Taken together, these results imply that future parvovirus B19 vaccines designed for children will require the use of conformationally preserved capsid proteins incorporating Th1 driving adjuvants. Furthermore, these data suggest novel mechanisms whereby parvovirus B19 infection may contribute to rheumatoid arthritis and unsuccessful pregnancy.
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页码:9903 / 9910
页数:8
相关论文
共 58 条
[1]   Interleukin 10 is a growth factor for a population of regulatory T cells [J].
Asseman, C ;
Powrie, F .
GUT, 1998, 42 (02) :157-158
[2]   Cell-mediated immune responses in four-year-old children after primary immunization with acellular pertussis vaccines [J].
Ausiello, CM ;
Lande, R ;
Urbani, F ;
la Sala, A ;
Stefanelli, P ;
Salmaso, S ;
Mastrantonio, P ;
Cassone, A .
INFECTION AND IMMUNITY, 1999, 67 (08) :4064-4071
[3]   Th1/Th2 cell dichotomy in acquired immunity to Bordetella pertussis: Variables in the in vivo priming and in vitro cytokine detection techniques affect the classification of T-cell subsets as Th1, Th2 or Th0 [J].
Barnard, A ;
Mahon, BP ;
Watkins, J ;
Redhead, K ;
Mills, KHG .
IMMUNOLOGY, 1996, 87 (03) :372-380
[4]  
BECK OE, 1981, CLIN EXP IMMUNOL, V43, P625
[5]   Quantitative analysis of neutralizing immune responses to human parvovirus B19 using a novel reverse transcriptase polymerase chain reaction based assay [J].
Bostic, JR ;
Brown, KE ;
Young, NS ;
Koenig, S .
JOURNAL OF INFECTIOUS DISEASES, 1999, 179 (03) :619-626
[6]   ANTIGENIC PARVOVIRUS B19 COAT PROTEINS VP1 AND VP2 PRODUCED IN LARGE QUANTITIES IN A BACULOVIRUS EXPRESSION SYSTEM [J].
BROWN, CS ;
SALIMANS, MMM ;
NOTEBORN, MHM ;
WEILAND, HT .
VIRUS RESEARCH, 1990, 15 (03) :197-211
[7]   ASSEMBLY OF EMPTY CAPSIDS BY USING BACULOVIRUS RECOMBINANTS EXPRESSING HUMAN PARVOVIRUS-B19 STRUCTURAL PROTEINS [J].
BROWN, CS ;
VANLENT, JWM ;
VLAK, JM ;
SPAAN, WJM .
JOURNAL OF VIROLOGY, 1991, 65 (05) :2702-2706
[8]  
Brown KE, 1997, MONOGR VIROL, V20, P42
[9]  
BROWN T, 1984, LANCET, V2, P1033
[10]   DIMINISHED INTERFERON-GAMMA AND LYMPHOCYTE-PROLIFERATION IN NEONATAL AND POSTPARTUM PRIMARY HERPES-SIMPLEX VIRUS-INFECTION [J].
BURCHETT, SK ;
COREY, L ;
MOHAN, KM ;
WESTALL, J ;
ASHLEY, R ;
WILSON, CB .
JOURNAL OF INFECTIOUS DISEASES, 1992, 165 (05) :813-818