title: Dichotomy between T Cell and B Cell Tolerance to Neonatal Retroviral Infection Permits T Cell Therapy.
abstract: Elucidation of the immune requirements for control or elimination of retroviral infection remains an important aim. We studied the induction of adaptive immunity to neonatal infection with a murine retrovirus, under conditions leading to immunological tolerance. We found that the absence of either maternal or offspring adaptive immunity permitted efficient vertical transmission of the retrovirus. Maternal immunodeficiency allowed the retrovirus to induce central Th cell tolerance in the infected offspring. In turn, this compromised the offspring's ability to mount a protective Th cell-dependent B cell response. However, in contrast to T cells, offspring B cells were not centrally tolerized and retained their ability to respond to the infection when provided with T cell help. Thus, escape of retrovirus-specific B cells from deletional tolerance offers the opportunity to induce protective retroviral immunity by restoration of retrovirus-specific T cell help, suggesting similar T cell immunotherapies for persistent viral infections.
authors.affiliation: Retroviral Immunology, The Francis Crick Institute, Mill Hill Laboratory, London NW7 1AA, United Kingdom.
authors.forename: Bettina
authors.identifier: 0000-0003-2047-6252
authors.initials: B
authors.lastname: Mavrommatis
authors.affiliation: Retroviral Immunology, The Francis Crick Institute, Mill Hill Laboratory, London NW7 1AA, United Kingdom.
authors.forename: Lucie
authors.initials: L
authors.lastname: Baudino
authors.affiliation: Retroviral Immunology, The Francis Crick Institute, Mill Hill Laboratory, London NW7 1AA, United Kingdom.
authors.forename: Prisca
authors.initials: P
authors.lastname: Levy
authors.affiliation: Retroviral Immunology, The Francis Crick Institute, Mill Hill Laboratory, London NW7 1AA, United Kingdom.
authors.forename: Julia
authors.initials: J
authors.lastname: Merkenschlager
authors.affiliation: Retroviral Immunology, The Francis Crick Institute, Mill Hill Laboratory, London NW7 1AA, United Kingdom.
authors.forename: Urszula
authors.initials: U
authors.lastname: Eksmond
authors.affiliation: Retroviral Immunology, The Francis Crick Institute, Mill Hill Laboratory, London NW7 1AA, United Kingdom.
authors.forename: Tiziano
authors.identifier: 0000-0003-1102-4668
authors.initials: T
authors.lastname: Donnarumma
authors.affiliation: Retrovirus-Host Interactions, The Francis Crick Institute, Mill Hill Laboratory, London NW7 1AA, United Kingdom; and.
authors.forename: George
authors.initials: G
authors.lastname: Young
authors.affiliation: Retrovirus-Host Interactions, The Francis Crick Institute, Mill Hill Laboratory, London NW7 1AA, United Kingdom; and.|Department of Medicine, Faculty of Medicine, Imperial College London, London SW7 2AZ, United Kingdom.
authors.forename: Jonathan
authors.identifier: 0000-0003-3377-323X
authors.initials: J
authors.lastname: Stoye
authors.affiliation: Retroviral Immunology, The Francis Crick Institute, Mill Hill Laboratory, London NW7 1AA, United Kingdom; george.kassiotis@crick.ac.uk.|Department of Medicine, Faculty of Medicine, Imperial College London, London SW7 2AZ, United Kingdom.
authors.forename: George
authors.initials: G
authors.lastname: Kassiotis
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000831:Animals, Newborn; D001402:B-Lymphocytes / Q000276:immunology* / Q000637:transplantation / Q000821:virology; D002478:Cells, Cultured; D061167:Central Tolerance; D005260:Female; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D009052:Leukemia Virus, Murine / Q000276:immunology*; D007942:Leukemia, Experimental / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011247:Pregnancy; D012192:Retroviridae Infections / Q000276:immunology / Q000517:prevention & control* / Q000635:transmission; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation / Q000821:virology; D014412:Tumor Virus Infections / Q000276:immunology / Q000517:prevention & control* / Q000635:transmission