TY - JOUR
T1 - The role of CD80/CD86 in generation and maintenance of functional virus-specific CD8+ T cells in mice infected with lymphocytic choriomeningitis virus
AU - Grujic, Mirjana
AU - Bartholdy, Christina
AU - Remy, Melissa
AU - Pinschewer, Daniel D
AU - Christensen, Jan P
AU - Thomsen, Allan Randrup
PY - 2010/8/1
Y1 - 2010/8/1
N2 - Lymphocytic choriomeningitis virus (LCMV)-specific CD8+ T cell responses are considered to be independent of CD28-B7 costimulation. However, the LCMV-specific response has never been evaluated in B7.1/B7.2-/- mice. For this reason, we decided to study the T cell response in B7.1/B7.2 -/- mice infected with two different strains of LCMV, one (Traub strain) typically causing low-grade chronic infection, and another (Armstrong clone 53b) displaying very limited capacity for establishing chronic infection. Using Traub virus we found that most B7.1/B7.2-/- mice were unable to rid themselves of the infection. Chronic infection was associated with a perturbed CD8+ T cell epitope hierarchy, as well as with the accumulation of cells expressing markers of terminal differentiation and being unable to respond optimally to Ag restimulation. Examination of matched CD28-/- mice revealed a similar albeit less pronounced pattern of CD8+ T cell dysfunction despite lack of virus persistence. Finally, analysis of B7.1/B7.2-/- mice infected with Armstrong virus revealed a scenario quite similar to that in Traub infected CD28-/- mice; that is, the mice displayed evidence of T cell dysfunction, but no chronic infection. Taken together, these results indicate that B7 costimulation is required for induction and maintenance of LCMV-specific CD8+ T cell memory, irrespective of the LCMV strain used for priming. However, the erosion of CD8+ T cell memory in B7.1/B7.2-/- mice was more pronounced in association with chronic infection. Finally, virus-specific T cell memory was more impaired in the absence of B7 molecules than in the absence of the CD28 receptor, supporting earlier data suggesting the existence of additional stimulatory receptors for B7.
AB - Lymphocytic choriomeningitis virus (LCMV)-specific CD8+ T cell responses are considered to be independent of CD28-B7 costimulation. However, the LCMV-specific response has never been evaluated in B7.1/B7.2-/- mice. For this reason, we decided to study the T cell response in B7.1/B7.2 -/- mice infected with two different strains of LCMV, one (Traub strain) typically causing low-grade chronic infection, and another (Armstrong clone 53b) displaying very limited capacity for establishing chronic infection. Using Traub virus we found that most B7.1/B7.2-/- mice were unable to rid themselves of the infection. Chronic infection was associated with a perturbed CD8+ T cell epitope hierarchy, as well as with the accumulation of cells expressing markers of terminal differentiation and being unable to respond optimally to Ag restimulation. Examination of matched CD28-/- mice revealed a similar albeit less pronounced pattern of CD8+ T cell dysfunction despite lack of virus persistence. Finally, analysis of B7.1/B7.2-/- mice infected with Armstrong virus revealed a scenario quite similar to that in Traub infected CD28-/- mice; that is, the mice displayed evidence of T cell dysfunction, but no chronic infection. Taken together, these results indicate that B7 costimulation is required for induction and maintenance of LCMV-specific CD8+ T cell memory, irrespective of the LCMV strain used for priming. However, the erosion of CD8+ T cell memory in B7.1/B7.2-/- mice was more pronounced in association with chronic infection. Finally, virus-specific T cell memory was more impaired in the absence of B7 molecules than in the absence of the CD28 receptor, supporting earlier data suggesting the existence of additional stimulatory receptors for B7.
KW - Animals
KW - Antigens, CD28
KW - Antigens, CD80
KW - Antigens, CD86
KW - CD8-Positive T-Lymphocytes
KW - Cell Differentiation
KW - Cell Division
KW - Epitopes, T-Lymphocyte
KW - Immunologic Memory
KW - Lymphocytic Choriomeningitis
KW - Lymphocytic choriomeningitis virus
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Mice, Transgenic
KW - Receptors, Antigen, T-Cell
U2 - 10.4049/jimmunol.0903894
DO - 10.4049/jimmunol.0903894
M3 - Journal article
C2 - 20601595
SN - 0022-1767
VL - 185
SP - 1730
EP - 1743
JO - Journal of Immunology
JF - Journal of Immunology
IS - 3
ER -