Exhaustion of CTL memory and recrudescence of viremia in lymphocytic choriomeningitis virus-infected MHC class II-deficient mice and B cell-deficient mice.
To study the contribution of CD4+ T cells and B cells to antiviral immunity and long term virus control, MHC class II-deficient and B cell-deficient mice were infected with lymphocytic choriomeningitis virus. In class II-deficient mice, which lack CD4+ T cells, the primary CTL response is virtually intact, and the infection is initially controlled in most organ sites including the blood. However, approximately 2 mo postinfection, CTL memory cannot be detected, and recrudescence of viremia to titers as high as seen during the acute phase of the infection is observed. To investigate whether this phenomenon could reflect participation of B cells and/or Abs in long term virus control, similar experiments were performed with mice that do not have mature B cells because of a disrupted membrane exon of the mu chain gene. In these mice, the cell-mediated immune response was slightly delayed, but transient virus control was observed in most mice. However, approximately 3 mo postinfection, blood virus titers were as high as observed during the acute infection, and no CTL memory could be demonstrated. These results indicate that Abs and/or B cells are required for permanent virus control and that in their absence, the virus-specific CTL potential becomes exhausted. Together our results indicate that while CD8+ cells play a dominant role in acute virus control, all three major components of the immune system are required for long term virus control.
Thomsen
A R
AR
Institute of Medical Microbiology and Immunology, University of Copenhagen, Denmark.
Johansen
J
J
Marker
O
O
Christensen
J P
JP
D000208:Acute Disease; D000361:Agammaglobulinemia / Q000150:complications / Q000276:immunology; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003289:Convalescence; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D007111:Immunity, Cellular; D007075:Immunoglobulin M / Q000172:deficiency; D007148:Immunoglobulin mu-Chains / Q000235:genetics; D007153:Immunologic Deficiency Syndromes / Q000150:complications / Q000276:immunology*; D007156:Immunologic Memory; D008216:Lymphocytic Choriomeningitis / Q000150:complications / Q000276:immunology* / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000302:isolation & purification; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014766:Viremia / Q000276:immunology* / Q000821:virology
D000949:Histocompatibility Antigens Class II; D007075:Immunoglobulin M; D007148:Immunoglobulin mu-Chains