CD4(+) T cell clones producing both interferon-gamma and interleukin-10 predominate in bronchoalveolar lavages of active pulmonary tuberculosis patients

The pattern of cytokine production in T cell clones derived from bronchoalv eolar lavages (BAL) of active pulmonary tuberculosis (TB) patients was anal yzed in clones obtained by limiting dilution procedures which expand with h igh efficiency either total T lymphocytes, independently of their antigen-r ecognition specificity, or Mycobacterium tuberculosis-specific T cells. BAL -derived clones, representative of CD4(+) cells from five patients with act ive TB, produced significantly higher amounts of TFN-gamma than BAL-derived CD4(+) clones from three inactive TB donors or four controls (with unrelat ed, noninfectious pathology). Average IL-4 and IL-10 production did not dif fer significantly in the three groups. Although these data suggest a predom inant Th1 response to M; tuberculosis infection in the lungs, the majority of BAL-derived CD4(+) clones produced both IFN-gamma and IL-10 and the perc entage of clones with this pattern of cytokine production was significantly higher in clones derived from BAL of active TB patients than from controls . Only rare clones derived from peripheral blood (PB)derived CD45RO(+) CD4( +) T cells of both patients (nine cases) and controls (four cases) produced both IFN-gamma and IL-10; instead, the IL-10-producing clones derived from . PB T cells most often also produced IL-4, displaying a typical Th2 phenot ype. Higher average amounts of lFN-gamma and IL-10 were produced by BAL-der ived CD8(+) clones of four active TB patients than of four controls, althou gh the frequency of CD8(+) clones producing both TFN-gamma and IL-10 was lo wer than that of CD4(+) clones. The M tuberculosis-specific BAL-derived T c ell clones from three active TB patients were almost exclusively CD4(+) and produced consistently high levels of IFN-gamma often in association with I L-10, but very rarely with IL-4. Unlike the BAL-derived clones, the M. tube rculosis-specific clones derived from PB CD45RO+ CD4+ T cells of three diff erent active TB patients and two healthy donors showed large individual var iability in cytokine production as well as in the proportion of CD4(+), CD8 (+), or TCR gamma/delta(+) clones. These results indicate the predominance of CD4(+) T cells producing both the proinflammatory cytokine IFN-gamma and the anti-inflammatory cytokine IL-10 in BAL of patients with active TB. (C ) 1999 Academic Press.