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

Dirk Homann, Antoinette Tishon, Dietmar P. Berger, William O. Weigle, Matthias G. Von Herrath, Michael B.A. Oldstone

Research output: Contribution to journalArticlepeer-review

144 Scopus citations

Abstract

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 μMT/μMT (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 (MHC) 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-γ) and interleukin 2, with differences most pronounced for CD8 T cells. While emphasizing the importance of CD4 T- cell help and IFN-γ 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.

Original languageEnglish
Pages (from-to)9208-9216
Number of pages9
JournalJournal of Virology
Volume72
Issue number11
DOIs
StatePublished - Nov 1998
Externally publishedYes

Fingerprint

Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this