Enhanced establishment of a virus carrier state in adult CD4+ T-cell-deficient mice.
CD4+ T cells play an important role in regulating the immune response; their contribution to virus clearance is variable. Mice that lack CD4+ T cells (CD4-/- mice) and are therefore unable to produce neutralizing antibodies cleared viscero-lymphotropic lymphocytic choriomeningitis virus (LCMV) strain WE when infected intravenously with a low dose (2 x 10(2) PFU) because of an effective CD8+ cytotoxic T-cell (CTL) response. In contrast, infection with a high dose (2 x 10(6) PFU) of LCMV strain WE led to expansion of antiviral CTL, which disappeared in CD4-/- mice; in contrast, CD4+ T-cell-competent mice developed antiviral memory CTL. This exhaustion of specific CTL caused viral persistence in CD4-/- mice, whereas CD4+ T-cell-competent mice eliminated the virus. After infection of CD4-/- mice with the faster-replicating LCMV strain DOCILE, abrogation of CTL response and establishment of viral persistence developed after infection with a low dose (5 x 10(2) PFU), i.e., an about 100-fold lower dose than in CD(4+)-competent control mice. These results show that absence of T help enhances establishment of an LCMV carrier state in selected situations.
Battegay
M
M
Department of Pathology, University of Zürich, Switzerland.
Moskophidis
D
D
Rahemtulla
A
A
Hengartner
H
H
Mak
T W
TW
Zinkernagel
R M
RM
D000818:Animals; D000914:Antibodies, Viral; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002353:Carrier State; D008216:Lymphocytic Choriomeningitis / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D009500:Neutralization Tests; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000914:Antibodies, Viral