CLONAL ANALYSIS OF CYTO-TOXIC LYMPHOCYTE-T RESPONSE TO AUTOLOGOUS HUMAN METASTATIC MELANOMA
CLONAL ANALYSIS OF CYTO-TOXIC LYMPHOCYTE-T RESPONSE TO AUTOLOGOUS HUMAN METASTATIC MELANOMA
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DOI：
10.1002/ijc.2910350518
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发表时间：
1985-01-01
影响因子：
6.4
通讯作者：
PARMIANI, G
中科院分区：
文献类型：
--
作者：
ANICHINI, A;FOSSATI, G;PARMIANI, G
Peripheral blood lymphocytes (PBL) from a melanoma (Me) patient, previously shown to be unable to react against the autologous tumor (Me 28) after mixed lymphocyte-tumor culture (MLTC), were cultured in vitro with the autologous tumor in MLTC and/or with IL-2-containing supernatants. T-cell clones were then obtained by limiting dilution and by micromanipulation. Eleven clones, selected for autologous tumor (Auto-Tu) cytotoxicity, were tested for specificity on a panel of 17 cell cultures of normal and neoplastic origin, revealing a complex spectrum of lytic activities. Three groups of clones could be identified depending on the patterns of cytotoxicity. One clone (B11.12) lysed Me28 and expressed a borderline reactivity against 1 allogeneic Me. A 2nd group of clones (A4, A4.18, H10, E12, C9) lysed the Auto-Tu and allogeneic Me. The last group of clones (A4.2, A4.3, A4.4, A7, B7) expressed a broader pattern of reactivity with significant cytotoxicity against targets of different histologic origin. Furthermore, the 2nd and 3rd groups of clones lysed K562 while B11.12 did not. The Auto-Tu-restricted reactivity of clone B11.12, confirmed by a further test on 13 allogeneic Me and on autologous IL-2 cultured lymphocytes, suggests the recognition of antigenic structures preferentially expressed on Me28. Blocking studies, performed with monoclonal antibodies (MAb), revealed that an anti-HLA class I MAb (w6/32), but not 2 anti-DR MAbs (L243, D1.12), could inhibit the cytotoxic activity of clones B11.12 on Me28. A significant blocking effect by w6/32 on Me28 was achieved also with clones A4.4 and H10 but not with clones A4.2, A4.3 and A7. The phenotype of all clones was T3+, T4-, T8+, HNK-1-, suggesting that the anti-tumor effectors were of the T-cell lineage. Taken together, it is apparently possible to isolate anti-tumor CTL-clones after MLTC from a PBL population of a metastatic melanoma patient. Furthermore, a role of class-I antigens in the interaction of some cloned effectors with the autologous tumor target is suggested.
