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 patients undergoing pericardiocentesis were assayed for proliferative response to purified protein derivative of Mycobacterium tuberculosis (PPD). Of the 23 patients tested, 10 had culture‐positive tuberculous effusions, while 13 had non‐tuberculous aetiologies. Three different kinetic responses were identified: (i) accelerated responses (found in 70% of EML from patients with culture‐positive tuberculous effusions); (ii) ‘flat’ responses (found in 10% of EML from patients with culture‐positive tuberculous effusions); and (iii) normal kinetic responses. These differences in kinetic response may reflect underlying immune mechanisms important in the immunopathogenesis of TB. In order to address this possibility we performed LDA on a selection of patients with culture‐positive extrapulmonary TB: three patients with accelerated responses, two with normal responses, and one with a ‘flat’ response. The results confirm the previously reported accumulation of PPD‐specific responder cells in the effusion of patients with TB. Cell‐mediated suppressor mechanisms (as shown by ‘V’‐shaped LDA curves) were found in the blood 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 may influence the outcome of infection.