Human thymocyte responsiveness to stem cell factor: synergy with interleukin-2 for the generation of NK/LAK cytotoxicity.
Human recombinant stem cell factor (SCF) increases the viability and cell size of a subset of thymocytes in vitro, but does not independently induce phenotypic changes on thymocytes indicative of T cell differentiation. The SCF-responsive thymocytes have characteristics of large granular cells, that do not express T, B or NK cell-related antigens, and are primarily found in immature thymocyte subsets. These large granular thymocytes do not display cytotoxic activity. However, SCF acts synergistically with IL-2 in the generation of cytotoxic effector cells from thymocyte precursors. Synergy in cytotoxicity is observed to both NK-sensitive and NK-resistant targets. Studies of the SCF receptors on thymocytes show that receptors are expressed on mature 'bright' CD3+ cells, immature 'dim' CD3+ cells as well as CD3- cells. IL-2 increases the frequency of SCF receptor-positive cells in cultured thymocytes, which may explain its synergy with SCF in the generation of NK/LAK cytotoxicity. These data show that SCF enhances the functional development of thymic NK/LAK cells in vitro.
Uittenbogaart
C H
CH
Department of Pediatrics, UCLA School of Medicine, USA.
Schmidc
I
I
Kiertscher
S
S
Shau
H
H
Anisman
D J
DJ
Zsebo
K M
KM
Clement
L T
LT
D015703:Antigens, CD / Q000032:analysis; D002454:Cell Differentiation; D002478:Cells, Cultured; D002648:Child; D003602:Cytotoxicity, Immunologic; D004357:Drug Synergism; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D015979:Killer Cells, Lymphokine-Activated; D007694:Killer Cells, Natural / Q000276:immunology*; D010641:Phenotype; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis; D019089:Stem Cell Factor / Q000494:pharmacology*; D013950:Thymus Gland / Q000166:cytology* / Q000187:drug effects / Q000276:immunology
D015703:Antigens, CD; D007376:Interleukin-2; D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit