Lymphocyte subsets and proliferation at presentation and during the therapeutic course of childhood tuberculosis. † 713

The lack of data on lymphocyte populations in childhood tuberculosis (TB) and inadequate knowledge of longitudinal changes of these cells in TB hamper our understanding of protective host responses to the world's most succesful bacterial pathogen. We therefore determined lymphocyte subsets (flow cytometry) and performed lymphoproliferative studies [to PHA, PPD and H37rv(virulent M. tuberculosis solute); thymidine incorporation] in 91 HIV-negative South African children with pulmonary TB (median age 39 mos., range 3-171). Patients were enrolled prospectively and evaluated after 6 wks. and 3 mos. of standard antituberculosis therapy. At baseline low lymphocyte subset numbers were common. The percentage of patients with decreased absolute lymphocyte numbers for age were: CD3 T cells 23%, CD4 T cells 33%, CD8 T cells 17%, CD19 B cells 29%, CD56 NK cells 45%. Decreased CD4 and CD8 T cells were associated with reduced lymphoproliferative indexes (LI) (p<0.001). Patients with culture positive TB (n=35) had lower LI compared to culture negative patients (p<0.01). This provided evidence for more severe immunosuppression in the presence of higher bacterial burdens and presumedly more severe disease. Marked increases in lymphocyte responses to mycobacterial antigens were demonstrated following therapy (p<0.001). CD3 T cell and NK cell numbers also increased (p<0.05 for all subsets) whereas B cell numbers decreased (p=0.2); however, not all subsets expanded equally. The largest increases occurred in CD8 T cells and NK cells (by a median factor 1.5 and 1.45, respectively, at 3 mos. compared to baseline, p<0.001 and p=0.008). Preferential CD8 T cell expansion resulted in decreasing CD4:CD8 T cell ratios over time (median 1.3 and 1.0 at presentation and 3 mos., respectively, p=0.016). This decrease in CD4:CD8 T cell ratio was surprising in view of the putative central role of CD4 T cells in protection against mycobacteria. Expansion of CD8 T cells (and NK cells) may point toward a protective role of these cells in immunity to M. tuberculosis.