HOST GENETIC-DETERMINANTS OF VACCINE-INDUCED EOSINOPHILIA DURING RESPIRATORY SYNCYTIAL VIRUS-INFECTION

Citation
T. Hussell et al., HOST GENETIC-DETERMINANTS OF VACCINE-INDUCED EOSINOPHILIA DURING RESPIRATORY SYNCYTIAL VIRUS-INFECTION, The Journal of immunology (1950), 161(11), 1998, pp. 6215-6222
Citations number
48
Categorie Soggetti
Immunology
ISSN journal
00221767
Volume
161
Issue
11
Year of publication
1998
Pages
6215 - 6222
Database
ISI
SICI code
0022-1767(1998)161:11<6215:HGOVED>2.0.ZU;2-7
Abstract
In BALB/c mice, sensitization with the attachment protein (G) of respi ratory syncytial virus (RSV) leads to CD4(+) T cell-mediated lung eosi nophilia during subsequent challenge with RSV, To determine the host g enetic influences on this model of lung eosinophilia, we tested 15 dif ferent inbred mouse strains, Eosinophilia developed in all H-2(d) (BAL B/c, DBA/2n, and B10.D2), but not in H-2(k) (CBA/Ca, CBA/J, C3H, BALB. K, or B10.BR) mouse strains. Among H-2(b) mice, 129 and BALB.B develop ed eosinophilia, whereas C57BL/6 and C57BL/10 did not. Testing first g eneration crosses between sensitive and resistant strains showed that eosinophilia developed in all H-2(dxk) (n = 5), irrespective of backgr ound genes, but not in H-2(dxb) (n = 2) mice. In vivo depletion of CD8 (+) T cells or IFN-gamma rendered C57BL/6, but not BALB.K mice, suscep tible to eosinophilia. Analysis of B10 recombinant mice showed that th e D-d allele (in B10.A(5R) mice) prevented CD8(+) T cell accumulation in the lung, resulting in intense lung eosinophilia, However, the Db a llele (in B10.A(2R) and B10.A(4R) mice) supported CD8(+) T cell expans ion and prevented eosinophilia. Intracellular cytokine staining showed that lung eosinophilia correlated with reduced IFN-gamma and increase d IL-10 expression in lung T cells. These results are compatible with the unifying model that Th2 cells mediate the disease but can be inhib ited by CD8(+) T cells secreting IFN-gamma. Our findings have importan t implications for the development of protective, nonpathogenic vaccin es for RSV disease.