CD40-CD40 ligand costimulation is required for generating antiviral CD4 T cell responses but is dispensable for CD8 T cell responses.
This study documents a striking dichotomy between CD4 and CD8 T cells in terms of their requirements for CD40-CD40 ligand (CD40L) costimulation. CD40L-deficient (-/-) mice made potent virus-specific CD8 T cell responses to dominant as well as subdominant epitopes following infection with lymphocytic choriomeningitis virus. In contrast, in the very same mice, virus-specific CD4 T cell responses were severely compromised. There were 10-fold fewer virus-specific CD4 T cells in CD40L-/- mice compared with those in CD40L+/+ mice, and this inhibition was seen for both Th1 (IFN-gamma, IL-2) and Th2 (IL-4) responses. An in vivo functional consequence of this Th cell defect was the inability of CD40L-/- mice to control a chronic lymphocytic choriomeningitis virus infection. This study highlights the importance of CD40-CD40L interactions in generating virus-specific CD4 T cell responses and in resolving chronic viral infection.
Whitmire
J K
JK
Emory Vaccine Center, Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Flavell
R A
RA
Grewal
I S
IS
Larsen
C P
CP
Pearson
T C
TC
Ahmed
R
R
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D019013:CD40 Antigens / Q000378:metabolism / Q000502:physiology*; D023201:CD40 Ligand; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D002908:Chronic Disease; D002999:Clone Cells; D004357:Drug Synergism; D018984:Epitopes, T-Lymphocyte / Q000032:analysis; D008024:Ligands; D008213:Lymphocyte Activation / Q000235:genetics; D008216:Lymphocytic Choriomeningitis / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
D019013:CD40 Antigens; D018984:Epitopes, T-Lymphocyte; D008024:Ligands; D008562:Membrane Glycoproteins; D023201:CD40 Ligand