CD4+ T cells and gamma interferon in the long-term control of persistent friend retrovirus infection

被引:47
作者
Iwashiro, M [1 ]
Peterson, K [1 ]
Messer, RJ [1 ]
Stromnes, IM [1 ]
Hasenkrug, KJ [1 ]
机构
[1] NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA
关键词
D O I
10.1128/JVI.75.1.52-60.2001
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
We have used the Friend virus model to determine the basic mechanisms by which the immune system can control persistent retroviral infections. Previously we showed that CD4(+) T cells play an essential role in keeping persistent retrovirus in check, The present in vitro experiments with a Friend virus-specific CD4(+) T-cell clone revealed that these cells produce gamma interferon (IPN-gamma), which acts with two distinct mechanisms of antiviral activity. First, IFN-gamma had a direct inhibitory effect on virus production. This inhibitory effect was noncytolytic and, interestingly, was not associated with decreased cell surface expression of viral antigens. The second mechanism of IFN-gamma -mediated antiviral activity was an enhancement of CD4(+) T-cell-mediated cytolytic activity. We also found an in vivo role for IFN-gamma in the control of persistent Friend virus infections, Neutralization of IFN-gamma in persistently infected mice resulted in significantly increased levels of virus in the spleen, and a significant percentage of IFN-gamma -deficient mice were unable to maintain long-term control over Friend virus infections.
引用
收藏
页码:52 / 60
页数:9
相关论文
共 52 条
[21]   Antigen-driven C-C chemokine-mediated HIV-1 suppression by CD4(+) T cells from exposed uninfected individuals expressing the wild-type CCR-5 allele [J].
Furci, L ;
Scarlatti, G ;
Burastero, S ;
Tambussi, G ;
Colognesi, C ;
Quillent, C ;
Longhi, R ;
Loverro, P ;
Borgonovo, B ;
Gaffi, D ;
Carrow, E ;
Malnati, M ;
Lusso, P ;
Siccardi, AG ;
Lazzarin, A ;
Beretta, A .
JOURNAL OF EXPERIMENTAL MEDICINE, 1997, 186 (03) :455-460
[22]   Noncytopathic clearance of lymphocytic choriomeningitis virus from the hepatocyte [J].
Guidotti, LG ;
Borrow, P ;
Brown, A ;
McClary, H ;
Koch, R ;
Chisari, FV .
JOURNAL OF EXPERIMENTAL MEDICINE, 1999, 189 (10) :1555-1564
[23]   Intracellular inactivation of the hepatitis B virus by cytotoxic T lymphocytes [J].
Guidotti, LG ;
Ishikawa, T ;
Hobbs, MV ;
Matzke, B ;
Schreiber, R ;
Chisari, FV .
IMMUNITY, 1996, 4 (01) :25-36
[24]   Viral clearance without destruction of infected cells during acute HBV infection [J].
Guidotti, LG ;
Rochford, R ;
Chung, J ;
Shapiro, M ;
Purcell, R ;
Chisari, FV .
SCIENCE, 1999, 284 (5415) :825-829
[25]   MECHANISM AND BIOLOGICAL SIGNIFICANCE OF CD4-MEDIATED CYTOTOXICITY [J].
HAHN, S ;
GEHRI, R ;
ERB, P .
IMMUNOLOGICAL REVIEWS, 1995, 146 :57-79
[26]   COMPARATIVE CLONAL ANALYSIS OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 (HIV-1)-SPECIFIC CD4+ AND CD8+ CYTOLYTIC LYMPHOCYTES-T ISOLATED FROM SERONEGATIVE HUMANS IMMUNIZED WITH CANDIDATE HIV-1 VACCINES [J].
HAMMOND, SA ;
BOLLINGER, RC ;
STANHOPE, PE ;
QUINN, TC ;
SCHWARTZ, D ;
CLEMENTS, ML ;
SILICIANO, RF .
JOURNAL OF EXPERIMENTAL MEDICINE, 1992, 176 (06) :1531-1542
[27]   Lymphocyte deficiencies increase susceptibility to friend virus-induced erythroleukemia in Fv-2 genetically resistant mice [J].
Hasenkrug, KJ .
JOURNAL OF VIROLOGY, 1999, 73 (08) :6468-6473
[28]   The role of CD4 and CD8 T cells in recovery and protection from retroviral infection: Lessons from the friend virus model [J].
Hasenkrug, KJ ;
Dittmer, U .
VIROLOGY, 2000, 272 (02) :244-249
[29]   Immunoprotective determinants in friend murine leukemia virus envelope protein [J].
Hasenkrug, KJ ;
Brooks, DM ;
Robertson, MN ;
Srinivas, RV ;
Chesebro, B .
VIROLOGY, 1998, 248 (01) :66-73
[30]   Immunity to retroviral infection: The Friend virus model [J].
Hasenkrug, KJ ;
Chesebro, B .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (15) :7811-7816