Cytotoxic T-cell activation by polyribonucleotides: DNA synthesis is not required.

Abstract

We have shown that cytotoxic T cells can be polyclonally activated by a short exposure to complexes of polyadenylic:polyuridylic acid (poly A:U). Activation is optimal at a dose of 100 microgram/ml poly A:U and occurs during a 2 h incubation period in the absence of antigen. Killing of allogeneic, but not syngeneic, target cells can be observed after 12 h in culture and peaks after 21-24 h in the absence of any nonspecific binding ligand. The observed cytotoxicity is mediated by T lymphocytes and dose not require accessory macrophages or DNA synthesis for the activation or expression of effector functions. These results suggest that few requirements exist for the activation of cytotoxic T cells.

Presence of Alloantigen‐Reactive Cells in Neonatally Tolerized Mice

“…In vitro expression of cytotoxicity without Con A included in the assay system was only possible when the activated cells were allogeneic to the targets [14]. A similar immunological specificity has been shown following in vitro activation using both Con A [2,9,14] and the polyclonal Tcell activator poly A:U [4]. Self-tolerance in these systems can be interpreted as a complete absence of clones capable of being activated by polyclonal T cell activators to express cytotoxicity to self-determinants, in accordance with the clonal elimination hypothesis.…”

A review of immunomodulators and their application in veterinary medicine

“…These substances, typically polyinosinic acid complexed with polycytidylic acid (poly I:C), or polyadenylic acid complexed with polyuridylic acid (poly A:U) are capable of inducing interferon production by lymphocytes (Vengris & Mare, 1972), presumably because they simulate viral genetic material. They have also been shown to affect such lymphocyte functions as antibody secretion (Han &Johnson, 1976) and cytotoxicity (Bick & Moller, 1977). These latter activities may reflect augmentation of T-helper cell function, possibly mediated by increased lymphokine secretion.…”

Modulation of the immune system by synthetic polynucleotides

“…Non-specific polyclonal activation of cytotoxic T cells by poly A : U has been charcterized by Bick and Moller [5]. Their experiments showed that after a 2 h incubation in the presence of poly A:U, activation occurred in as short a time interval as 12-24 h. This occurred in the absence of antigen and independent of DNA synthesis.…”