Regulation of human cytotoxic T lymphocyte development by IL-7.
The effects of IL-7 on the generation of human CTL in alloantigen-, virus-, and lectin-stimulated systems were examined. Addition of IL-7 at the onset of cultures resulted in marked (up to 80-fold) augmentation of cytotoxicity accompanied by smaller (1.5- to 4-fold) increases in total lymphocyte number. Studies of CTL development in purified lectin-stimulated CD8+ T cell populations demonstrated that IL-7 could act directly on the CD8+ lymphocyte subset to augment cytotoxicity. In MLC, the IL-7-induced enhancement of cytotoxicity was found to be mediated primarily by the CD8+ subpopulation of lymphocytes. Late addition of IL-7 (day 5 of 7) resulted in an increase in cytolytic activity that was associated with little or no increase in total or activated CD8+ lymphocyte number indicating that IL-7 may act as a differentiation factor for human CTL. A role for endogenous IL-7 in CTL development was suggested by the observation that addition of neutralizing antiserum to IL-7 to MLC at initiation (or 5 days thereafter) resulted in decreased levels of cytotoxicity. These results indicate that IL-7 can exert major up-regulatory effects on human CTL development and suggest that these effects are both proliferative and differentiative.
Hickman
C J
CJ
Laboratory of Cellular Immunology, Food and Drug Administration, Bethesda, MD 20892.
Crim
J A
JA
Mostowski
H S
HS
Siegel
J P
JP
D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D016827:CD8 Antigens; D003208:Concanavalin A / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004950:Esterases / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular; D007156:Immunologic Memory; D066298:In Vitro Techniques; D009980:Influenza A virus / Q000276:immunology; D015851:Interleukin-7 / Q000494:pharmacology / Q000502:physiology*; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology*; D013997:Time Factors
D000945:Antigens, Differentiation, T-Lymphocyte; D016827:CD8 Antigens; D015851:Interleukin-7; D003208:Concanavalin A; D004950:Esterases; C022635:serine esterase