Helper T cell-independent proliferation of CD8+ cytotoxic T lymphocytes transduced with an IL-1 receptor retrovirus.
Although the proliferation of CD8+ CTL typically requires cytokine support provided by helper T cells, a subset of naturally occurring CD8+ CTL are capable of proliferating independently of T cell help. Such helper-independent CTL have previously been shown to possess IL-1 receptors (IL-1R) and to proliferate in response to IL-1 through endogenous production of IL-2. In this study, we have transduced conventional helper-dependent CTL clones with a retroviral vector encoding the murine type I IL-1R. Transduced CTL selected in G418 expressed vector-derived transcripts encoding IL-1R and displayed approximately 1000 cell surface receptors with an IL-1 affinity typical for the type I IL-1R. In contrast to parental cells, transduced CTL proliferated in response to IL-1 in the presence of Ag, without a requirement for helper T cells, IL-2, or other cytokine support. Stimulation with both IL-1 and Ag was necessary for the proliferative response. No endogenous synthesis of IL-2 could be detected in the IL-1R transduced cells in response to IL-1 stimulation, in the presence or absence of Ag. The IL-1R-induced phenotype was demonstrated in two independent T cell clones, both of which retained Ag-specific cytolytic activity. No such conversion to a helper-independent phenotype was induced by a retroviral vector encoding only the neo gene. The behavior of the IL-1R-transduced CTL in proliferation assays thus resembled that of the naturally occurring helper-independent CTL.
Nagoya
S
S
Department of Medicine, University of Washington, Seattle 98101.
Greenberg
P D
PD
Yee
C
C
Weisser
K E
KE
Sugawara
H
H
Widmer
M B
MB
Slack
J
J
Dower
S K
SK
Lupton
S D
SD
Overell
R W
RW
D000818:Animals; D016827:CD8 Antigens / Q000032:analysis; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D015870:Gene Expression; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics; D017472:Receptors, Interleukin-1 / Q000235:genetics*; D012190:Retroviridae; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014162:Transfection
D016827:CD8 Antigens; D007376:Interleukin-2; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D015847:Interleukin-4