Suppression of in vitro lymphocyte DNA synthesis by killed Pseudomonas aeruginosa

Abstract

Whole antibiotic-killed classic Pseudomonas aeruginosa organisms elicited human lymphocyte [3H]thymidine (TdR) uptake in vitro after 5 days in culture. However, high concentrations of the same preparation did not elicit [3H]TdR incorporation. The investigation of this lymphocyte unresponsiveness revealed that a high dose of P. aeruginosa, when added to lymphocyte cultures together with optimal concentrations of lymphocyte activators (e.g., plant lectins or whole killed Staphylococcus aureus Cowan 1), caused a potent, nonspecifically expressed inhibition of lymphocyte [3H]TdR uptake in response to these mitogens. High doses of P. aeruginosa were not cytotoxic to lymphocytes, and the inhibition caused was reversed when lymphocytes were washed free of bacteria. The inhibition of [3H]TdR uptake by high-dose P. aeruginosa did not require the generation of adherent suppressor cells or prostaglandin-mediated, steroid-sensitive or radiation-sensitive suppressor mechanisms. At optimal lymphocyte stimulatory concentrations of P. aeruginosa, the addition of indomethacin or the depletion of adherent cells caused an increase in lymphocyte [3H]TdR incorporation. This is consistent with an adherent-cell population regulating [3H]TdR uptake in response to P. aeruginosa via a prostaglandin-dependent pathway. This population was not involved in the inhibition of lymphocyte [3H]TdR uptake by high concentrations of P. aeruginosa.