Proliferative and cytolytic potentials of purified human tumor-infiltrating t lymphocytes. Impaired response to mitogen-driven stimulation despite T-cell receptor expression
✍ Scribed by S. Miescher; M. Stoeck; L. Qiao; C. Barras; L. Barrelet; V. von Fliedner
- Publisher
- John Wiley and Sons
- Year
- 1988
- Tongue
- French
- Weight
- 935 KB
- Volume
- 42
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Using limiting dilution analysis (LDA) we have previously shown that in most instances, the frequency (F) of proliferative T lymphocyte precursors (PTL-P) was strikingly reduced in tumor-infiltrating lymphocytes (TIL). In this study involving 19 cases, we show that the impaired clonogenic potential of CD2+ TlLs is primarily caused by an intrinsic defect rather than to suppressor T cells or to a direct effect of the tumor cells usually present in the culture system. This was demonstrated by experiments in which the F of PTL-Ps was quantitated both in highly purified CD2' TlLs (using a cell-sorter) and in non-purified TIL suspensions (still containing tumor cells), which originated from the same biopsy specimen. The F of PTL-Ps was virtually identical in either sorted or nonsorted suspensions and the data from LDA were always consistent with the single-hit Poisson model, indicating that no suppressor cells interfered with growth of CD2 + TIL. Stimulation of sorted CD2+ TIL in low-density cultures by either phytohemagglutinin or anti-CD3-monoclonal antibody (MAb) indicated that the antigen-dependent activation pathway was impaired, although structurally intact T-cell receptor (TCR) complexes were apparently expressed, as assessed by immunofluorescence. The depressed proliferative response of CD2 + TIL could not be reversed in vitro when phorbol-esters were used in combination with ionomycin, which bypass the TCR. Nevertheless, 180 clones obtained from 8 cases were analyzed for their cytolytic activity. The majority mediated specific lytic activity (against unknown antigens), as assessed by lectindependent cell cytotoxicity, whereas only 6% of them manifested lymphokine-activated killing on appropriate targets.