Inhibition of erythroid progenitor growth is mediated by cytotoxic lymphocytes and not by natural killer cells or IFN-gamma.
Alloantigen primed T cells (PTC) were recovered from MLR at day 6 and 12, then added to cultures of erythroid progenitors, erythroid burst-forming units, BFU-E. The PBMC source of BFU-E was prepared either to retain or deplete APC by treatment with appropriate mAb and C. BFU-E grown in cocultures were counted at day 14 and replicate cultures assayed for IFN-gamma production on days 1 to 7. Analysis of MLR cells indicated that large, rapidly cycling cells recovered from MLR at day 6 have significant NK activity, whereas CTL activity is minimal, and production of IFN-gamma requires reexposure to APC. The smaller, noncycling cells recovered from MLR at day 12 have comparable NK activity, also require reexposure to APC for IFN-gamma production, but in addition have significant CTL activity. The addition of day 12 MLR cells to BFU-E cultures results in MHC restricted inhibition of BFU-E growth, suggesting that the CTL activity and not the NK activity contained within this population of cells is responsible for BFU-E inhibition. Studies using enriched population of BFU-E indicated that appropriate APC are needed to trigger both IFN-gamma production and BFU-E inhibition by the PTC. By using various APC-BFU-E combinations it was determined that after reexposure of PTC to appropriate APC, the inhibition of BFU-E was still target-specific indicating a direct effect between the PTC and BFU-E.
Torok-Storb
B
B
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
Graf
L
L
Shankar
P
P
D000328:Adult; D000938:Antigen-Presenting Cells / Q000276:immunology; D002460:Cell Line; D002470:Cell Survival; D003114:Colony-Forming Units Assay; D004912:Erythrocytes / Q000276:immunology / Q000502:physiology; D004920:Erythropoiesis; D006412:Hematopoietic Stem Cells / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007165:Immunosuppression Therapy; D007371:Interferon-gamma / Q000096:biosynthesis / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000502:physiology; D008213:Lymphocyte Activation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000502:physiology
D007371:Interferon-gamma