Premium
MHC class‐I‐restricted auto‐tumor‐specific CD4 + CD8 − T‐cell clones established from autologous mixed lymphocyte‐tumor‐cell culture (MLTC)
Author(s) -
Wang P.,
Vànky F.,
Klein E.
Publication year - 1992
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910510621
Subject(s) - cytotoxic t cell , cd8 , biology , ctl* , clone (java method) , t lymphocyte , microbiology and biotechnology , immunology , tumor infiltrating lymphocytes , antigen , cancer research , in vitro , biochemistry , dna
Autologous mixed lymphocyte‐tumor cell cultures (MLTC) were initiated with cytokine (IFNγ and TNFα)‐treated ex‐vivo tumor cells of lung, ovarian, breast and stomach carcinomas. The cytokine‐treated tumors expressed class‐l but not class‐M molecules. Although the proportion of CD8 + lymphocytes increased in the bulk culture of MLTCs, in 5/7 experiments the majority of the established T‐cell clones were CD4 + . Among the CD8 + clones a high proportion (77%) was cytotoxic, while the proliferative response was more frequent among the CD4 + clones (70%). In 4/26 cytotoxic T‐lymphocyte (CTL) clones (3/17 CD4 + and I /9 CD8 + ), derived from a patient with class l + class II − stomach carcinoma, lysis was restricted to the autologous tumor cells. These auto‐tumor‐specific clones did not lyse the autologous ConA blasts, the 5 allogeneic ex‐vivo tumors, the NK‐sensitive K562 or the relatively sensitive Daudi cells. The cytotoxicity of these clones was inhibited by pre‐incubation of the tumor cells with W6/32 (α‐class I) MAb, or by preincubation of the lymphocytes with OKT3 (α‐CD3) MAb. The α‐CD4 (OKT4) MAb had only a marginal effect on the CD4 + clones, while the lytic function of the CD8 + clone was inhibited by the α‐CD8 (OKT8) MAb. The 3 CD4 + CTL clones also responded with proliferation to the autologous tumor cells. This proliferative response was inhibited by the presence of W6/32 MAb. Our results indicate that the auto‐tumor lysis exerted by CD4 + CTL clones was restricted by the class‐l antigens, and that the CD4 molecules of the clones were not essential for the lytic interaction. © 1992 Wiley‐Liss. Inc .