Affiliation:
1. Cellular Cytotoxicity Laboratory, The Austin Research Institute, Heidelberg 3084, Victoria, Australia
Abstract
ABSTRACT
Mouse cytotoxic T lymphocytes (CTL) reactive with a H-2D
b
-presented 9-mer peptide of the human papillomavirus type 16 protein E7
49-57
(RAHYNIVTF) were generated from the spleen cells of wild-type C57BL/6 (B6) or B6 perforin-deficient (B6.P
0
) mice. CD8
+
B6 CTL displayed peptide-specific perforin- and Fas-mediated lysis of E7-transfected mouse RMA lymphoma cells (RMA-E7), while CD8
+
CTL from B6.P
0
mice lysed RMA-E7 cells via Fas ligand (FasL) exclusively. Rapid and efficient lysis of syngeneic bystander B6 blasts or RMA cells by either B6 or B6.P
0
Ag-activated CTL was mediated by a FasL-Fas mechanism. Fas-resistant bystanders were not lysed, nor were allogeneic Fas-sensitive C3H/HeJ (
H-2
k
) or BALB/c (
H-2
d
) bystander blasts. Interestingly, however, phorbol myristate acetate-ionomycin preactivation of B6.P
0
effectors enabled lysis of allogeneic
H-2
k
and
H-2
d
bystanders even in the absence of antigenic stimulation. Lysis of syngeneic bystander cells was always FasL-Fas dependent and required effector-bystander contact and, in particular, an interaction between CTL LFA-1 and bystander ICAM-1. Thus, in the context of major histocompatibility complex class I molecule-peptide ligation of the T-cell receptors of CD8
+
CTL, neighboring bystander cells that are syngeneic and Fas sensitive and express the adhesion molecule ICAM-1 are potential targets of CTL attack.
Publisher
American Society for Microbiology
Subject
Virology,Insect Science,Immunology,Microbiology
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