T-cell intrinsic expression of MyD88 is required for sustained expansion of the virus-specific CD8+ T-cell population in LCMV-infected mice.
Acute infection with lymphocytic choriomeningitis virus (LCMV) normally results in robust clonal expansion of virus-specific CD8(+) T cells, which in turn control the primary infection. However, similar infection of myeloid differentiation factor 88 (MyD88)-deficient mice leads to a markedly impaired T-cell response and chronic infection. It has been found previously that impairment of the innate immune response is not sufficient to explain this profound change in outcome. Using adoptive transfer of CD8(+) T cells, this study demonstrated unequivocally that T-cell expression of MyD88 is critical for a normal T-cell response to LCMV. In addition, it was found that expression of MyD88 is superfluous during early activation and proliferation of the antigen-activated CD8(+) T cells, but plays a critical role in the sustained expansion of the antigen-specific CD8(+) T-cell population during the primary T-cell response. Interestingly, a critical role for MyD88 was evident only under conditions of systemic infection with virus capable of causing prolonged infection, suggesting that MyD88 expression may function as an internal regulator of the threshold for antigen-driven, exhaustive differentiation.
Bartholdy
Christina
C
Institute of International Health, Immunology and Microbiology, University of Copenhagen, The Panum Institute, 3C Blegdamsvej, Copenhagen, DK-2200, Denmark.
Christensen
Jeanette E
JE
Institute of International Health, Immunology and Microbiology, University of Copenhagen, The Panum Institute, 3C Blegdamsvej, Copenhagen, DK-2200, Denmark.
Grujic
Mirjana
M
Institute of International Health, Immunology and Microbiology, University of Copenhagen, The Panum Institute, 3C Blegdamsvej, Copenhagen, DK-2200, Denmark.
Christensen
Jan P
JP
Institute of International Health, Immunology and Microbiology, University of Copenhagen, The Panum Institute, 3C Blegdamsvej, Copenhagen, DK-2200, Denmark.
Thomsen
Allan R
AR
Institute of International Health, Immunology and Microbiology, University of Copenhagen, The Panum Institute, 3C Blegdamsvej, Copenhagen, DK-2200, Denmark.
D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D005838:Genotype; D053590:Interleukin 1 Receptor Antagonist Protein / Q000172:deficiency; D018655:Lymphocyte Count; D008216:Lymphocytic Choriomeningitis / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology*; D053724:Receptors, Interleukin-18 / Q000172:deficiency; D013601:T-Lymphocytes / Q000276:immunology*; D018800:Thy-1 Antigens / Q000276:immunology; D051193:Toll-Like Receptors / Q000276:immunology
D053590:Interleukin 1 Receptor Antagonist Protein; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D053724:Receptors, Interleukin-18; D018800:Thy-1 Antigens; D051193:Toll-Like Receptors