Dynamic regulation of T cell immunity by CD43.
During a viral response, Ag-specific effector T cells show dramatically increased binding by the mAb 1B11 and the lectin peanut agglutinin (PNA). We investigated the contribution of CD43 expression to 1B11 and PNA binding as well as its role in generation and maintenance of a CD8 T cell response. Analysis of CD43(-/-) mice revealed no increased 1B11 binding and reduced PNA binding on virus-specific CD8 T cells from -/- mice compared with +/+ mice. Furthermore, we examined the role of CD43 in the kinetics of an immune response. We show that CD43 expression modestly effects generation of a primary virus-specific CD8 T cell response in vivo but plays a more significant role in trafficking of CD8 T cells to tissues such as the brain. More interestingly, CD43 plays a role in the contraction of the immune response, with CD43(-/-) mice showing increased numbers of Ag-specific CD8 T cells following initial expansion. Following the peak of expansion, Ag-specific CD8 T cells from -/- mice show similar proliferation but demonstrate increased Bcl-2 levels and decreased apoptosis of Ag-specific effector CD8 T cells in vitro. Consistent with a delay in the down-modulation of the immune response, following chronic viral infection CD43(-/-) mice show increased morbidity. These data suggest a dynamic role of CD43 during an immune response: a positive regulatory role in costimulation and trafficking of T cells to the CNS and a negative regulatory role in the down-modulation of an immune response.
Onami
Thandi M
TM
Emory Vaccine Center and Department of Microbiology and Immunology, Department of Surgery, Emory School of Medicine, Atlanta, GA 30322, USA.
Harrington
Laurie E
LE
Williams
Matthew A
MA
Galvan
Marisa
M
Larsen
Christian P
CP
Pearson
Thomas C
TC
Manjunath
N
N
Baum
Linda G
LG
Pearce
Brad D
BD
Ahmed
Rafi
R
D000818:Animals; D015703:Antigens, CD; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D002908:Chronic Disease; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D007111:Immunity, Cellular / Q000235:genetics; D007156:Immunologic Memory / Q000235:genetics; D051917:Leukosialin; D008213:Lymphocyte Activation / Q000235:genetics; D018655:Lymphocyte Count; D008216:Lymphocytic Choriomeningitis / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000473:pathology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D019887:Peanut Agglutinin / Q000037:antagonists & inhibitors / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D012795:Sialoglycoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology / Q000821:virology
D015703:Antigens, CD; D051917:Leukosialin; D019887:Peanut Agglutinin; D019253:Proto-Oncogene Proteins c-bcl-2; D012795:Sialoglycoproteins; C497863:Spn protein, mouse