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
| Autor: | Michael B. A. Oldstone, William O. Weigle, Matthias von Herrath, Dietmar P. Berger, Dirk Homann, Antoinette Tishon |
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| Rok vydání: | 1998 |
| Předmět: |
CD4-Positive T-Lymphocytes
Interleukin 2 Adoptive cell transfer Lymphocyte Cooperation Immunology Viral Pathogenesis and Immunity CD8-Positive T-Lymphocytes In Vitro Techniques Lymphocytic Choriomeningitis Major histocompatibility complex Immunotherapy Adoptive Microbiology Epitopes Interferon-gamma Mice Antigen Virology medicine Animals Lymphocytic choriomeningitis virus Cytotoxic T cell Antigens Viral B cell Mice Knockout B-Lymphocytes biology Mice Inbred C57BL CTL medicine.anatomical_structure Insect Science biology.protein Interleukin-2 Immunologic Memory CD8 medicine.drug |
| Zdroj: | Journal of Virology. 72:9208-9216 |
| ISSN: | 1098-5514 0022-538X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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