Cytotoxic CD8+ T lymphocytes reactive with human immunodeficiency virus-1 produce granulocyte/macrophage colony-stimulating factor and variable amounts of interleukins 2, 3, and 4 following stimulation with the cognate epitope.
Infection with human immunodeficiency virus type 1 (HIV-1) induces vigorous and persistent cytotoxic CD8+ T cell responses. CTL clones were derived from peripheral blood or cerebrospinal fluid of three HIV-1 patients, with depressed CD4+ T cell counts. When stimulated with HLA-compatible target cells (B-LCL) presensitized with cognate HIV-1 peptides, all clones produced GM-CSF, TNF-alpha, and IFN-gamma and most produced low amounts of IL2, IL3, and IL4. After nonspecific stimulation with a phorbol ester and calcium ionophore, the clones secreted cytokines at levels similar to those from CD4+ lines from an HIV-1 infected donor. The ability of supernatants from the stimulated CTL clones to support the formation of granulocyte-macrophage colonies in normal bone marrow suggests that the GM-CSF was biologically active. Release of cytokines by activated CTL may influence the immunopathogenesis of HIV disease.
Price
P
P
Infectious Disease Unit, Massachusetts General Hospital, Boston.
Johnson
R P
RP
Scadden
D T
DT
Jassoy
C
C
Rosenthal
T
T
Kalams
S
S
Walker
B D
BD
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D000001:Calcimycin / Q000494:pharmacology; D002460:Cell Line; D002999:Clone Cells; D000939:Epitopes; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism*; D007377:Interleukin-3 / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism*; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism / Q000821:virology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000939:Epitopes; D007376:Interleukin-2; D007377:Interleukin-3; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D000001:Calcimycin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D013755:Tetradecanoylphorbol Acetate