Influence of T cells on the expression of lymphokine-activated killer cell activity and in vivo tissue distribution

Abstract

Lymphokine-activated killer (LAK) cells are currently being evaluated in several cancer centers for the immunotherapy of patients with a variety of cancers. Understanding the in vivo distribution of LAK cells should help to optimize their antitumor efficacy. As a model system to examine this issue, nylon wool column-passed rat lymphocytes were cultured in the presence of rIL-2 for 1 and 2 days. The resulting cells were divided into two populations; one that adhered to the plastic flasks and the second which did not adhere. The adherent cells were found to be highly cytotoxic against NK-sensitive and NK-resistant targets, whereas the nonadherent cells were unable to kill NK-resistant targets unless T cells were removed from this population. These results indicate that T cells present in IL-2 activated bulk splenocytes may interfere with the activity of LAK cells. Adherent or nonadherent LAK cells were evaluated for their pattern of in vivo distribution after i.v. inoculation. These cells were found to display a restricted pattern of distribution, localizing mainly in the lungs at 2 h after i.v. injection but redistributing into the liver and the spleen by 24 h. LAK cells were rarely recovered from the lymphoid tissues, including the peripheral lymph nodes and the mesenteric lymph nodes. However, if T cells were not removed from the LAK cell population, some radioactivity was recovered from the peripheral and mesenteric lymph nodes. Fractionation of 2 day-activated, nonadherent population on discontinuous Percoll resulted in the enrichment of large granular lymphocyte (LGL)/LAK activity in low density fractions (42% and 45% Percoll), whereas high density fraction (70% Percoll) contained T cells which showed no cytolytic activity. Upon transfer into syngeneic rats, the 42% fraction showed typical LAK migration. In contrast, the 70% fraction showed typical T cell migration. What is more important, removal of the granulated cells resulted in a population which have no granules and resemble large agranular lymphocytes known to be pre-LGL/LAK cells. Large agranular lymphocytes showed a pattern of distribution different from both T and LGL/LAK cells.