Reactivity of peripheral blood leukocytes against human foetal cells. II. Cytotoxic potential of preparations enriched or depleted of different leukocyte populations.

Abstract

Leukocytes separated initially by Ficoll-Triosil sedimentation from the peripheral blood of 62 healthy donors and 64 patients with a variety of cancers were tested for cytotoxicity against cells from a single human foetal lung, by means of a microplate technique based on visual enumeration of surviving target cells. Under these conditions cytotoxicity was primarily observed to be a function of the granulocyte content of the preparations, which was extremely variable (range 0-60%). When the influence of these cells was greatly diminished through depletion by adherence, residual cytotoxicity was still detectable in the majority of samples tested. Complete abrogation of this cytotoxicity by pretreatment with carrageenan implicated cells of the monocyte-macrophage series, which persisted as a small minority (about 2%) in the already depleted effector cell populations. However some cytotoxicity could also be demonstrated in populations, purified by passage through columns containing nylon fibre or Degalan-coated (human Ig-anti Ig) beads, which consisted almost exclusively (about 98%) of lymphocytes, mainly of thymus (T)-dependent type (greater than or equal to 80%). Under these conditions and those in which T-cells were concentrated by formation of spontaneous E rosettes, cytotoxicity appeared to decline with T cell enrichment, suggesting that the cytolytic effects were attributable to cells of the non T-compartment which were present to a variable extent in the different T-cell-enriched populations. Although the absolute identity of these cells was not established, the experiments illustrate potential sources of non-specific cytotoxicity among different effector cell populations against target cells expressing antigens to which the majority of leukocyte donors--in health or disease--were presumably non-sensitized. As such these data have several implications for the interpretation of in vitro cytotoxicity tests against human neoplasms.