Evidence for an underlying CD4 helper and CD8 T-cell defect in B-cell-deficient mice:: Failure to clear persistent virus infection after adoptive immunotherapy with virus-specific memory cells from μMT/μMT mice

被引:140
作者
Homann, D
Tishon, A
Berger, DP
Weigle, WO
von Herrath, MG
Oldstone, MBA
机构
[1] Scripps Res Inst, Dept Neuropharmacol, Div Virol, La Jolla, CA 92037 USA
[2] Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA
关键词
D O I
10.1128/JVI.72.11.9208-9216.1998
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Adoptive transfer of virus-specific memory lymphocytes can be used to identify factors and mechanisms involved in the clearance of persistent virus infections. To analyze the role of B cells in clearing persistent infection with lymphocytic choriomeningitis virus (LCMV), we used B-cell-deficient mu MT/mu MT (B-/-) mice, B-/- mice controlled an acute LCMV infection with the same kinetics and efficiency as B-cell-competent (B+/+) mice via virus-specific, major histocompatibility complex (MIIC) class I restricted CD8(+) cytotoxic T lymphocytes (CTL), CTL from B-/- and B+/+ mice were equivalent in affinity to known LCMV CTL epitopes and had similar CTL precursor frequencies (pCTL), Adoptive transfer of memory cells from B+/+ mice led to virus clearance from persistently infected B+/+ recipients even after in vitro depletion of B cells, indicating that B cells or immunoglobulins are not required in the transfer population. In contrast, transfer of memory splenocytes from B-/- mice Failed to clear virus. Control of virus was restored neither by transferring higher numbers of pCTL nor by supplementing B-/- memory splenocytes with LCMV-immune B cells or immune sera. Instead, B-/- mice were found to have a profound CD4 helper defect, Furthermore, compared to cultured splenocytes from B+/+ mice, those from B-/- mice secreted less gamma interferon (IFN-gamma) and interleukin 2, with differences most pronounced for CD8 T tells. While emphasizing the importance of CD4 T-cell help and IFN-gamma in the control of persistent infections, the CD4 T-helper and CD8 T-cell defects in B-/- mice suggest that B cells contribute to the induction of competent T effector cells.
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页码:9208 / 9216
页数:9
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