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Blood, Vol. 95 No. 9 (May 1), 2000:
pp. 2883-2889
Killer inhibitory receptor (CD158b) modulates the lytic activity
of tumor-specific T lymphocytes infiltrating renal cell carcinomas
Nadia Guerra,
Maryvonne Guillard,
Eric Angevin,
Hamid Echchakir,
Bernard Escudier,
Alessandro Moretta,
Salem Chouaib, and
Anne Caignard
From INSERM U487, Institut Fédératif de Recherche
(IFR54), Institut Gustave Roussy, Villejuif, France; and Dipartimento
di Medicina Sperimentale, Universita degli Studi di Genova, Genova,
Italy.
In this study, we showed that renal tumors contain substantial
subsets of CD8+ p58+ T cells. From 1 of
these tumors, T cells were amplified in mixed lymphocytes-tumor cell
cultures and p58+ T cells were selected immunologically.
After expansion, phenotypic and functional features of
p58+ and p58 T cells were examined. The
p58+ T cells expressed p58.2 receptor and corresponded to
CD3+, CD8+, T-cell receptor (TCR)
 / + T cells that were CD56+ and
CD28. Functionally, p58+ T cells showed a
low level of lytic activity against autologous tumor cells that was
dramatically and specifically increased by anti-p58.2 monoclonal
antibody. On the other hand, p58 CD8+ T
cells did not lyse autologous tumor cells and had non-major histocompatibility complex-restricted cytotoxicity against K562 and
Daudi cells. A p58+ cytotoxic T lymphocyte (CTL) clone
(4C7) with the same characteristics as the p58+ T-cell
line was derived. This CTL clone did not lyse autologous normal B cells
but lysed several HLA-A1+ renal tumor cell lines.
Analysis of TCR repertoire diversity showed that the p58+
T-cell line contained 3 TCR rearrangements, whereas the TCR repertoire of p58 T cells was polyclonal. Interestingly, TCR
transcripts of p58+ T cells and of CTL clone 4C7 were
detected as prominent ex vivo in tumor cells but not in peripheral
blood mononuclear cells, suggesting that these cells are antigen
specific and amplified at the tumor site.
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