TY - JOUR
T1 - Allosensitization in IL-2-containing limiting dilution cultures generates cytotoxic T lymphocytes (CTL) rather than LAK cells reactive with a syngeneic nonimmunogenic murine tumor
AU - Leshem, Benny
AU - Epstein, Eyal
AU - Kedar, Eli
PY - 1989/1/15
Y1 - 1989/1/15
N2 - We have previously demonstrated that high frequency 1 20 of potent cytotoxic cells reactive with the nonimmunogenic lymphoma PIR-2 of C57BL/6 (B6, H-2b) origin, can be obtained by allosensitization of syngeneic B6 splenocytes against BALB/c (H-2d splenocytes in limiting dilution cultures (LDC). Since a high concentration (250 U/ml) of exogenous interleukin 2 (IL-2), sufficient for the elicitation of lymphokine-activated killer (LAK) cells, was used in the LDC, and because the LDC-derived cytotoxic cells were active against a wide spectrum of target cells, we investigated whether the anti PIR-2 effector cells are LAK cells or cytotoxic T lymphocytes (CTL). We found that depletion from the B6 responder cell population of Lyt2+ (CTL precursors), but not of asialo GM1+ (LAK cell precursors), prior to LDC, results in the ablation of anti PIR-2 activity. When B6 splenocytes were plated in LDC with IL-2, in the absence of allogeneic stimulating cells, the resulting anti PIR-2 activity was >10- to 500-fold lower than that obtained in LDC in the presence of allogeneic stimulating cells and IL-2. These and other observations suggest that the cytotoxic response against syngeneic tumors elicited by alloantigens in LDC is mediated by CTL rather than LAK cells, and that allogeneic sensitization in LDC can provide a means for the generation of CTL against syngeneic, nonimmunogenic tumors.
AB - We have previously demonstrated that high frequency 1 20 of potent cytotoxic cells reactive with the nonimmunogenic lymphoma PIR-2 of C57BL/6 (B6, H-2b) origin, can be obtained by allosensitization of syngeneic B6 splenocytes against BALB/c (H-2d splenocytes in limiting dilution cultures (LDC). Since a high concentration (250 U/ml) of exogenous interleukin 2 (IL-2), sufficient for the elicitation of lymphokine-activated killer (LAK) cells, was used in the LDC, and because the LDC-derived cytotoxic cells were active against a wide spectrum of target cells, we investigated whether the anti PIR-2 effector cells are LAK cells or cytotoxic T lymphocytes (CTL). We found that depletion from the B6 responder cell population of Lyt2+ (CTL precursors), but not of asialo GM1+ (LAK cell precursors), prior to LDC, results in the ablation of anti PIR-2 activity. When B6 splenocytes were plated in LDC with IL-2, in the absence of allogeneic stimulating cells, the resulting anti PIR-2 activity was >10- to 500-fold lower than that obtained in LDC in the presence of allogeneic stimulating cells and IL-2. These and other observations suggest that the cytotoxic response against syngeneic tumors elicited by alloantigens in LDC is mediated by CTL rather than LAK cells, and that allogeneic sensitization in LDC can provide a means for the generation of CTL against syngeneic, nonimmunogenic tumors.
KW - CTL
KW - IL-2
KW - LAK cells
KW - Limiting dilutions
UR - http://www.scopus.com/inward/record.url?scp=0024586275&partnerID=8YFLogxK
U2 - 10.1016/0165-2478(89)90068-0
DO - 10.1016/0165-2478(89)90068-0
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C2 - 2785493
AN - SCOPUS:0024586275
SN - 0165-2478
VL - 20
SP - 53
EP - 58
JO - Immunology Letters
JF - Immunology Letters
IS - 1
ER -