To analyze the statuses of CD8⁺ T cell exhaustion in patients with human immunodeficiency virus (HIV) infection, Mycobacterium tuberculosis (MTB) infection and co-infection.

A total of 87 patients infected with HIV and/or MTB in Wuxi Fifth People′s Hospital and Taicang First People′s Hospital from August 2019 to January 2020 were enrolled, including 18 cases of HIV infection, 34 cases of active tuberculosis (ATB), 19 cases of latent tuberculosis infection (LTB), seven cases of HIV coinfected with ATB, and nine cases of HIV coinfected with LTB. Another 11 healthy controls were also included. The peripheral blood of all subjects was collected for cell surface staining and intracellular cytokine staining, and flow cytometry was used to detect the expressions of activation molecules including CD62 ligand, CD44 and CD127, the transcription factor like eomesodermin (EOMES), T cell factor 1 (TCF-1), T-box expressed in T cells (T-bet), B lymphocyte-induced maturation protein 1 (Blimp-1), inhibitory receptors including programmed death-1 (PD-1) and T-cell immunoglobulin and mucin domain 3 (Tim-3) on CD8⁺ T cells. Mann-Whitney U test was used for statistical analysis.

The mean fluorescence intensities (MFIs) of the activation molecules CD62 ligand and CD44 in the HIV group were lower than those in the healthy control group, while the inhibitory receptor Tim-3 was higher than that in the healthy control group. The differences were all statistically significant (U=31.00, 1.00 and 0.00, respectively, all P<0.010). The MFIs of CD62 ligand and CD44 in HIV coinfected with LTB group were lower than those in LTB group, while PD-1 and Tim-3 were higher than those in LTB group. The differences were all statistically significant (U=4.00, 26.00, 6.00 and 3.00, respectively, all P<0.010). The MFIs of CD62 ligand, CD44 and CD127 in HIV coinfected with ATB group were lower than those in ATB group, while PD-1 and Tim-3 were higher than those in ATB group. The differences were all statistically significant (U=9.00, 40.00, 45.50, 28.00 and 7.00, respectively, all P<0.010). The proportion of terminal effector CD8⁺ T cells in the HIV group was higher than that in the healthy control group, while the proportion of central memory CD8⁺ T cells was lower than that in the healthy control group. The differences were both statistically significant (U=15.00 and 33.00, respectively, both P<0.010). The proportion of terminal effector CD8⁺ T cells in the HIV coinfected with LTB group was higher than the LTB group, while the proportion of central memory CD8⁺ T cells was lower than that in the LTB group. The differences were both statistically significant (U=7.00 and 20.00, respectively, both P<0.010). The proportion of terminal effector CD8⁺ T cells in the HIV coinfected with ATB group was higher than that in ATB group, while the proportion of central memory CD8⁺ T cells was lower than that in ATB group. The differences were statistically significant (both U=7.00, P<0.001). The expression level of PD-1⁺ Tim-3⁺ T cells in HIV group was higher than that in healthy control group, that in HIV coinfected with LTB group was higher than that in LTB group, and that in HIV coinfected with ATB group was higher than that in ATB group. The differences were all statistically significant (U=21.00, 6.00 and 5.50, respectively, all P<0.001). The MFI of transcription factors EOMES and TCF-1 in HIV coinfected with LTB group were lower than those in HIV group, while the MFI of T-bet was higher than that in HIV group. The differences were all statistically significant (U=3.00, 4.00 and 9.00, respectively, all P<0.001). The MFI of EOMES and TCF-1 in HIV coinfected with ATB group were lower than those in HIV group, while the MFI of T-bet and Blimp-1 were higher than those in the HIV group. The differences were all statistically significant (U=11.00, 14.00, 7.00 and 22.00, respectively, all P<0.050).

MTB co-infected with HIV patients present lower immune function and a higher degree of CD8⁺ T cell exhaustion. In addition, HIV patients co-infected with LTB and ATB have a higher degree of CD8⁺ T cell exhaustion than HIV infected patients.

HIV; Mycobacterium tuberculosis; Persistent infection; Coinfection; CD8⁺ T cells exhaustion