CONCISE COMMUNICATIONS Sequestration of T Lymphocytes to Body Fluids in Tuberculosis: Reversal of Anergy following Chemotherapy

The specificity of CD4 T lymphocytes was investigated in 6 patients affected by tuberculosis who had negative tuberculin purified protein derivative (PPD) skin tests at diagnosis. Polyclonal CD4 T cell lines from the peripheral blood failed to proliferate to PPD and to the 16or 38-kDa proteins of Mycobacterium tuberculosis, while CD4 cell lines from the disease site responded to PPD and to the 16- and 38-kDa proteins and derived epitopes in vitro. Four months after chemotherapy, the patients became responsive to PPD. The proliferative response to PPD and to the 16- or 38-kDa proteins and their derived peptides decreased in CD4 T cell lines from the disease site and increased in lines from the peripheral blood. These results indicate that CD4 T cells recognizing a vast array of M. tuberculosis epitopes are compartmentalized at the site of disease in anergic patients but appear in peripheral blood after chemotherapy. Depressed cell-mediated responses (anergy) often occur in patients affected by tuberculosis (TB). These include depressed lymphocyte proliferation to tuberculin purified protein derivative (PPD) in vitro and antigen-induced production of interferon-g [2, 3], which is associated with negative skin test reactivity to PPD in vivo [1] and in vitro. The cause of this phenomenon is probably multifactorial, with production of suppressive cytokines, such as interleukin (IL)‐10 [4] or transforming growth factor (TGF)‐b [5], defective antigen presentation in acute disease [6], and compartmentalization of CD4 T lymphocytes at the site of disease [4, 7, 8] all contributing. To investigate whether sequestration of Mycobacterium tuberculosis (MTB)‐specific T lymphocytes may account for the anergy observed in TB, we compared the responses of CD4 T lymphocytes from peripheral blood and from inflammatory sites of patients with TB anergy with defined epitopes from the MTB 16- and 38-kDa antigens.