Virus-induced polyclonal B cell activation improves protective CTL memory via retained CD27 expression on memory CTL.
Different viruses elicit distinct phenotypes of memory cytotoxic T lymphocytes (CTL). This is reflected in differential expression of homing receptors and costimulatory molecules like CD27. Memory CTL retained CD27 following lymphocytic choriomeningitis virus (LCMV) infection, but not after immunization with recombinant vaccinia virus or tumor cells expressing LCMV glycoprotein. Stable CD27 expression on memory CTL required ligation by CD70 expressed on polyclonally activated B cells during the contraction phase. The functional consequence of CD27 expressed on virus-specific CTL was analyzed in CD27-deficient mice. LCMV infection of CD27(-/-) mice revealed that primary CTL activation and expansion as well as elimination of the virus were independent of CD27 expression. In contrast, ligation of CD27 on memory CTL upon secondary antigen encounter increased clonal expansion and improved protection against re-infection. This points to novel B cell-CTL interactions during viral infection and to a beneficial role of polyclonal B cell activation that represents a characteristic of murine LCMV, human immunodeficiency virus and human hepatitis B and C virus infection.
Matter
Matthias
M
Department of Clinical Research, University of Berne, Bern, Switzerland.
Mumprecht
Sabine
S
Pinschewer
Daniel D
DD
Pavelic
Viktor
V
Yagita
Hideo
H
Krautwald
Stefan
S
Borst
Jannie
J
Ochsenbein
Adrian F
AF
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D053282:CD27 Ligand; D049109:Cell Proliferation; D002999:Clone Cells; D006801:Humans; D007156:Immunologic Memory; D008213:Lymphocyte Activation / Q000276:immunology*; D008216:Lymphocytic Choriomeningitis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015398:Signal Transduction / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D048069:Tumor Necrosis Factors / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology
D015703:Antigens, CD; D053282:CD27 Ligand; C505771:CD70 protein, human; C505772:Cd70 protein, mouse; D008565:Membrane Proteins; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D048069:Tumor Necrosis Factors