KINETICS OF PURIFIED PROTEIN DERIVATIVE (PPD) PROLIFERATION REFLECTS UNDERLYING SUPPRESSOR MECHANISMS REVEALED BY LIMITING DILUTION ANALYSIS (LDA) IN PATIENTS WITH EXTRAPULMONARY TUBERCULOSIS (TB)

Mononuclear leucocytes from the blood (PBML) and effusion (EML) of pat ients undergoing pericardiocentesis were assayed for proliferative res ponse to purified protein derivative of Mycobacterium tuberculosis (PP D). Of the 23 patients tested, 10 had culture-positive tuberculous eff usions, while 13 had non-tuberculous aetiologies. Three different kine tic responses were identified: (i) accelerated responses (found in 70% of EML from patients with culture-positive tuberculous effusions); (i i) 'flat' responses (found in 10% of EML from patients with culture-po sitive tuberculous effusions); and (iii) normal kinetic responses. The se differences in kinetic response may reflect underlying immune mecha nisms important in the immunopathogenesis of TB. In order to address t his possibility we performed LDA on a selection of patients with cultu re-positive extrapulmonary TB: three patients with accelerated respons es, two with normal responses, and one with a 'flat' response. The res ults confirm the previously reported accumulation of PPD-specific resp onder cells in the effusion of patients with TB. Cell-mediated suppres sor mechanisms (as shown by 'V'-shaped LDA curves) were found in the b lood of one patient and the effusion of another. In both cases 'flat' PPD-proliferative responses were observed. However, the LDA data also suggested the presence of in vivo mechanisms limiting the clonal burst size. Thus it appears that immune responses in extrapulmonary TB are influenced by an array of inhibitory mechanisms, modulation of which m ay influence the outcome of infection.