CD40 ligand-deficient mice generate a normal primary cytotoxic T-lymphocyte response but a defective humoral response to a viral infection.
CD40 ligand is expressed on activated T cells and interacts with CD40 on B cells and monocytes. It is not known what role CD40 ligand plays in the generation of immune responses to viral infection. To address this issue, we examined virus-specific T- and B-cell responses in CD40 ligand-deficient (CD40L-/-) mice following infection with lymphocytic choriomeningitis virus (LCMV). We found that primary anti-LCMV specific antibody responses were severely impaired in CD40L-/- mice, with the defect being most striking for antibody of the immunoglobulin G1 (IgG1) isotype. Interestingly, low levels of LCMV-specific antibodies of the IgG2a, IgG2b, and IgG3 isotypes were made in the CD40L-/- mice, showing that IgG1 responses are totally dependent on CD40L but that at least some IgG2a, IgG2b, and IgG3 responses can be CD40L independent. However, unlike CD40L+/+ mice, CD40L-/- mice were unable to sustain virus-specific antibody responses and showed a gradual decline in serum antibody levels over time. The CD40L-/- mice were also deficient in the generation of memory B cells. In contrast to the severely impaired humoral responses, CD40L-/- mice generated potent virus-specific CD8+ cytotoxic T-lymphocyte responses after LCMV infection and were able to clear the virus. These results show that CD40L does not play a role in generating primary virus-specific CD8+ cytotoxic T-lymphocyte responses but does affect the primary antibody response and the generation of memory B cells.
Whitmire
J K
JK
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Slifka
M K
MK
Grewal
I S
IS
Flavell
R A
RA
Ahmed
R
R
D000208:Acute Disease; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D000917:Antibody Formation / Q000276:immunology; D023201:CD40 Ligand; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002522:Chlorocebus aethiops; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D017353:Gene Deletion; D007074:Immunoglobulin G / Q000276:immunology; D008216:Lymphocytic Choriomeningitis / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D014709:Vero Cells
D000914:Antibodies, Viral; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D023201:CD40 Ligand