Studies of sublines selected for loss of HLA expression from an EBV-transformed lymphoblastoid cell line. Changes in sensitivity to cytotoxic T cells activated by allostimulation and natural killer cells activated by IFN or IL-2.
Murine tumor studies have suggested that variations in MHC class I expression may influence the behavior of tumor cells in vivo. Corresponding human tumor studies remain at the descriptive level but they show differences in MHC Ag expression between and even within tumors. Our purpose was to explore possible functional relationships between class I expression and sensitivity to different forms of cell-mediated lysis in a potentially immunogenic system: EBV-immortalized B cells. Their cytotoxic sensitivity was tested to CTL and to IFN- or IL-2-activated effector cells. The wild-type line (high class I) was sensitive to CTL with the appropriate Ag restriction, but resisted lysis by normal or IFN-activated PBL. In contrast, HLA loss variants showed a reduced sensitivity to CTL and an increased NK sensitivity. The latter could be related to the loss of class I molecules: an intermediate (haplotype loss) expressor variant was moderately NK sensitive, whereas a weak expressor line, with an additional down-regulation of the remaining haplotype, was highly sensitive. IL-2-activated PBL ("LAK") cells showed the same killing pattern as NK cells, although the levels of lysis were generally higher. These data support the hypothesis that the MHC class I Ag expression-dependent, CTL-mediated lysis is complemented by additional mechanisms, mediated by effectors that recognize cells with reduced MHC Ag expression that would otherwise escape CTL-mediated rejection.
Ohlén
C
C
Department of Tumor Biology, Karolinska Institute, Stockholm, Sweden.
Bejarano
M T
MT
Grönberg
A
A
Torsteinsdottir
S
S
Franksson
L
L
Ljunggren
H G
HG
Klein
E
E
Klein
G
G
Kärre
K
K
D002460:Cell Line; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D002999:Clone Cells / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D005434:Flow Cytometry; D006680:HLA Antigens / Q000032:analysis*; D004854:Herpesvirus 4, Human; D006801:Humans; D007372:Interferons / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D006680:HLA Antigens; D007376:Interleukin-2; D007372:Interferons