CD40L-deficient mice show deficits in antiviral immunity and have an impaired memory CD8+ CTL response.
The ligand for CD40 (CD40L) is expressed on the surface of activated CD4+ T cells and its role in T-B cell collaborations and thymus-dependent humoral immunity is well established. Recently, by generating CD40L-knockout mice, we have confirmed its previously described role in humoral immunity and defined another important function of this molecule in the in vivo clonal expansion of antigen-specific CD4+ T cells. Here, we investigated the potential in vivo role of CD40L in antiviral immunity by examining the immune response mounted by CD40L-deficient mice following infection with lymphocytic choriomeningitis virus (LCMV), Pichinde virus, or vesicular stomatitis virus. Humoral immune responses of CD40L-deficient mice to these viruses were severely compromised, although moderate titres of antiviral IgM and some IgG2a were produced by virus-infected CD40L-deficient mice by a CD4+ T cell-independent mechanism. By contrast, CD40L-deficient mice made strong primary CTL responses to all three viruses. Interestingly however, although memory CTL activity was detectable in CD40L-deficient mice two months after infection with LCMV, the memory CTL response was much less efficient than in wild-type mice. Together, the results show that CD40-CD40L interactions are required for strong antiviral humoral immune responses, and reveal a novel role for CD40L in the establishment and/or maintenance of CD8+ CTL memory.
Borrow
P
P
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037, USA.
Tishon
A
A
Lee
S
S
Xu
J
J
Grewal
I S
IS
Oldstone
M B
MB
Flavell
R A
RA
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology*; D023201:CD40 Ligand; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000145:classification; D007075:Immunoglobulin M / Q000096:biosynthesis; D007156:Immunologic Memory; D016219:Immunotherapy, Adoptive; D008562:Membrane Glycoproteins / Q000172:deficiency*; D051379:Mice; D018345:Mice, Knockout; D012016:Reference Values; D018353:Rhabdoviridae Infections / Q000276:immunology* / Q000473:pathology; D013154:Spleen / Q000276:immunology / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology*
D000914:Antibodies, Viral; D019013:CD40 Antigens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008562:Membrane Glycoproteins; D023201:CD40 Ligand