CD 137 is a Useful Marker for Identifying CD 4 + T Cell Responses to Mycobacterium tuberculosis

Upregulation of CD 137 on recently activated CD 8 + T cells has been used to identify rare viral and tumour antigen‐specific T cells from the peripheral blood. We aimed to evaluate the accuracy of CD 137 for identifying Mycobacterium tuberculosis (Mtb)‐reactive CD 4 + T cells in the peripheral blood of infected individuals by flow cytometry and to investigate the characteristics of these CD 137 + CD 4 + T cells. We initially enrolled 31 active tuberculosis ( TB ) patients, 31 individuals with latent TB infection ( LTBI ) and 25 healthy donors. The intracellular CD 137 and interferon‐ γ ( IFN ‐ γ ) production by CD 4 + T cells was simultaneously detected under unstimulated and CFP 10‐stimulated (culture filtrate protein 10, a Mtb‐specific antigen) conditions. In unstimulated CD 4 + T cells, we found that the CD 137 expression in the TB group was significantly higher than that in the LTBI group. Stimulation with CFP 10 largely increased the CD 4 + T cell CD 137 expression in both the TB and LTBI groups. After CFP 10 stimulation, the frequency of CD 137 + CD 4 + T cells was higher than that of IFN ‐ γ + CD 4 + T cells in both the TB and LTBI groups. Most of the CFP 10‐activated IFN ‐ γ ‐secreting cells were CD 137‐positive, but only a small fraction of the CD 137‐positive cells expressed IFN ‐ γ . An additional 20 patients with TB were enrolled to characterize the CD 45 RO + CCR 7 + , CD 45 RO + CCR 7 − and CD 45 RO − subsets in the CD 137 + CD 4 + T cell populations. The Mtb‐specific CD 137 + CD 4 + T cells were mainly identified as having an effector memory phenotype. In conclusion, CD 137 is a useful marker that can be used for identifying Mtb‐reactive CD 4 + T cells by flow cytometry.