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Medientyp:
E-Artikel
Titel:
CD4+ T cells specific for a model latency‐associated antigen fail to control a gammaherpesvirus in vivo
Beteiligte:
Smith, Christopher M.;
Rosa, Gustavo T. L.;
May, Janet S.;
Bennett, Neil J.;
Mount, Adele M.;
Belz, Gabrielle T.;
Stevenson, Philip G.
Erschienen:
Wiley, 2006
Erschienen in:European Journal of Immunology
Sprache:
Englisch
DOI:
10.1002/eji.200636164
ISSN:
0014-2980;
1521-4141
Entstehung:
Anmerkungen:
Beschreibung:
<jats:title>Abstract</jats:title><jats:p>CD4<jats:sup>+</jats:sup> T cells play a major role in containing herpesvirus infections. However, their cellular targets remain poorly defined. <jats:italic>In vitro</jats:italic> CD4<jats:sup>+</jats:sup> T cells have been reported to kill B cells that harbor a latent gammaherpesvirus. We used the B cell‐tropic murine gammaherpesvirus‐68 (MHV‐68) to test whether this also occurred <jats:italic>in vivo</jats:italic>. MHV‐68 that expressed cytoplasmic ovalbumin (OVA) in tandem with its episome maintenance protein, ORF73, stimulated CD8<jats:sup>+</jats:sup> T cells specific for the H2‐K<jats:sup>b</jats:sup>‐restricted OVA epitope SIINFEKL and was rapidly eliminated from C57BL/6 (H2<jats:sup>b</jats:sup>) mice. However, the same virus failed to stimulate CD4<jats:sup>+</jats:sup> T cells specific for the I‐A<jats:sup>d</jats:sup>/I‐A<jats:sup>b</jats:sup>‐restricted OVA<jats:sub>323–339</jats:sub> epitope. We overcame any barrier to the MHC class II‐restricted presentation of an endogenous epitope by substituting OVA<jats:sub>323–339</jats:sub> for the CLIP peptide of the invariant chain (ORF73‐IRES‐Ii‐OVA), again expressed in tandem with ORF73. This virus presented OVA<jats:sub>323–339</jats:sub> but showed little or no latency deficit in either BALB/c (H2<jats:sup>d</jats:sup>) or C57BL/6 mice. Latent antigen‐specific CD4<jats:sup>+</jats:sup> T cells therefore either failed to recognize key virus‐infected cell populations <jats:italic>in vivo</jats:italic> or lacked the effector functions required to control them.</jats:p>