A longitudinal study of in vitro IFN gamma production and cytotoxic T cellresponses of tuberculosis patients in The Gambia

Setting: This study was carried out at the MRC Laboratories, The Gambia. Objectives: To characterize the antigen-specific IFN gamma production and c ytotoxic T cell (CTL) responses of patients during active tuberculosis, tre atment, and following recovery. Design: PBMC were isolated from 37 patients with tuberculosis and incubated with either PPD, live M. bovis BCG, or no antigen and IFN gamma production measured after 7 days. CTL activity agains t these antigens was determined using autologous antigen-pulsed monocyte-de rived macrophages as target cells. A subset of these patients (7-18 dependi ng on antigen and assey used) were tested 2 months into drug treatment and 3 months after discharge. A group of blood bank donors (n = 21) were also t ested to evaluate IFN gamma responses in endemic controls; a subset (n = 16 ) were also tested for CTL activity. Results: The ability to produce IFN gamma in response to mycobacterial anti gens correlated with the Mantoux skin test status of the patient. IFN gamma production to live M. bovis BCG was diminished at diagnosis but returned a fter 2 months of drug treatment, and was sustained after completion of drug therapy. The CTL responses to both PPD and live M. bovis BCG were reduced during the period of drug treatment compared to those at diagnosis, but ret urned to the original levels after recovery. Conclusions: Drug treatment induced marked alterations in the immune respon ses of tuberculosis patients with induction of IFN gamma production in resp onse to stimulation with live M. bovis BCG. This may indicate activation of both CD4 and CD8 T cells. (C) 2000 Harcourt Publishers Ltd.