Influence of cystic fibrosis plasma on lymphocyte responses to Pseudomonas aeruginosa in vitro.

Abstract

Peripheral blood lymphocytes from cystic fibrosis (CF) patients with advanced diseases do not proliferate following exposure to Pseudomonas aeruginosa (PA) antigen sin in vitro. In this study, we sought to determine if CF lymphocyte unresponsiveness to PA is due to inhibitory factors present in CF plasma. Nineteen low-responder CF (LRCF) patients increased their mean lymphocyte proliferative response (l3H]thymidine incorporation) from 703 +/- 133 to 3178 +/- 811 net cpm when incubated in normal plasma. These increase do not reach the level of response seen in normal individuals (8510 +/- 1323 net cpm). Ten of 19 patients did not increase their responses over 2000 net cpm. Plasma from LRCF patients does not inhibit responses of normal or homologous CF lymphocytes. Responses of normal individual in autologous plasma were 7807 +/- 1164 net cpm. Th same lymphocytes incubated in 16 plasmas from LRCF patients gave responses of 7146 +/- 1317 net cpm. Preincubation of the PA antigen in LRCF plasma increases rather than inhibits normal lymphocyte responses. LRCF plasma absorbed with PA no longer supports normal lymphocyte responses to PA. LRCF and normal plasma mixtures increase responses of normal lymphocytes to PA over responses in autologous plasma. Extensive preincubation and washing of LRCF lymphocytes to eliminate blocking immune complexes failed to restore the ability to respond to PA. These data suggest that the unresponsiveness to PA of lymphocytes from CF patients with advanced disease is due to alterations occurring at a cellular level in vivo. This lymphocyte dysfunction cannot be reversed by normal plasma in vitro, nor can it be induced in normal lymphocytes by the use of CF plasma.