Complement component 3 is required for optimal expansion of CD8 T cells during a systemic viral infection.
In addition to its established role in innate immune mechanisms, complement component C3 is also of critical importance in B cell activation and T cell-dependent Ab responses. In this study, we have examined the requirement for C3 in the generation of primary CD8 T cell responses to an acute systemic viral infection. We compared Ag-specific CD8 T cell responses to lymphocytic choriomeningitis virus (LCMV) between wild-type (+/+) and C3-deficient (C3(-/-)) mice on both 129/B6 and B6 backgrounds. These studies revealed that C3 activity is required for optimal expansion of LCMV-specific effector CD8 T cells in an epitope-dependent fashion, which is influenced by the genetic background of the mice. Studies in complement receptor 1/2 (CR1/CR2)-deficient mice showed that regulation of LCMV-specific CD8 T cell responses by C3 is not dependent upon CR1/CR2. These findings may have implications in vaccine development, therapy of autoimmune diseases, and prevention of graft rejection.
Suresh
M
M
Department of Pathobiological Sciences, University of Wisconsin, Madison 53706, USA. sureshm@svm.vetmed.wisc.edu
Molina
Hector
H
Salvato
Maria S
MS
Mastellos
Dimitrios
D
Lambris
John D
JD
Sandor
Matyas
M
D000208:Acute Disease; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D003176:Complement C3 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics; D008216:Lymphocytic Choriomeningitis / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011951:Receptors, Complement / Q000172:deficiency / Q000235:genetics; D017464:Receptors, Complement 3d / Q000172:deficiency / Q000235:genetics
D003176:Complement C3; D018984:Epitopes, T-Lymphocyte; D011951:Receptors, Complement; D017464:Receptors, Complement 3d