In vivo expression of perforin by CD8+ lymphocytes during an acute viral infection.
CTL and NK cells cultured in vitro have been shown to contain a cytolytic pore-forming protein (PFP/perforin/cytolysin). To date, it has not been determined whether perforin is expressed by CTL that have been primed in vivo. Here, we have infected mice with two strains of lymphocytic choriomeningitis virus (LCMV), one of which mainly produces choriomeningitis and, the other, hepatitis. Brain and liver cryostat sections obtained from LCMV-infected mice were stained for various lymphocyte markers, including perforin. We were able to detect a large accumulation of perforin antigen in CD8+/Thy-1+/asialo GM1+/CD4- lymphocytes, which in fact represent the main infiltrating cell type found in brain and liver sections obtained during the late acute stage of LCMV infection. Perforin was also detected in a smaller population of CD8-/asialo GM1+/NK 1.1+/F480- cells, presumably corresponding to NK cells. Perforin-positive cells were found to have the morphology of blasts or large granular lymphocytes (LGL). These observations, together with in vitro studies performed in the past, indicate that perforin may be associated exclusively with LGL-like CTL blasts and NK cells. Our results demonstrate for the first time the presence of perforin in CTL that have been primed in vivo and suggest that perforin-positive CTL may be directly involved in producing the immunopathology associated with the LCMV infection.
Young
L H
LH
Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston 02114.
Klavinskis
L S
LS
Oldstone
M B
MB
Young
J D
JD
D000208:Acute Disease; D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte; D016827:CD8 Antigens; D002465:Cell Movement; D000939:Epitopes / Q000032:analysis; D005677:G(M1) Ganglioside; D006028:Glycosphingolipids; D007106:Immune Sera; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008216:Lymphocytic Choriomeningitis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000032:analysis / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D054353:Perforin; D010641:Phenotype; D052899:Pore Forming Cytotoxic Proteins; D013194:Staining and Labeling; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D014018:Tissue Distribution
D000945:Antigens, Differentiation, T-Lymphocyte; D016827:CD8 Antigens; D000939:Epitopes; D006028:Glycosphingolipids; D007106:Immune Sera; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside