Objective: To investigate the frequencies of immunologically competent cells (ICCs) in the liver-infiltrating lymphocytes (LILs) and peripheral blood and their possible role in pathogenesis in patients with chronic severe hepatitis B (CSHB).
Methods: LILs were isolated from the liver tissue samples from 11 CSHB patients and 5 normal controls (NCs) by the method of combined grinding with semi-frosted microscopic slides and sedimentation of hepatic cells. The frequency of isolated ICCs, including CD3(+), CD4(+), and CD8(+) T-cells, NK cells, NKT cells, and B cells was examined and compared with that of the circulating ICCs in the CSHB patients. Comparison was conducted between the CSHB patients and the controls.
Results: (1) In the CSHB patients, the frequencies of CD4(+) T cells and B cells in LILs were 17% +/- 6% and 3.0% +/- 1.0% respectively, both significantly lower than those in the circulating blood (32% +/- 8% and 21.4% +/- 12.2% respectively, both P < 0.01); however, the frequencies of CD8(+) T cells, NK cells, and NKT cells in LILs were 38% +/- 13%, 34% +/- 18%, and 10% +/- 4% respectively, all significantly lower than those in the circulating blood (26% +/- 6%, 15% +/- 9%, and 6% +/- 4%, all P < 0.05). (2) The frequencies of infiltrating CD3(+) T cells and CD4(+) T cells of the CSHB patients were both significantly higher than those of the NCs (P = 0.042 and P = 0.001); and the frequency of infiltrating CD8(+) T cells of the CSHB patients was higher than that of the NCs, and the and the frequencies of infiltrating NK cells and NKT cells in LILs were lower than those of the NCs, however, not significantly. (3) Compared with the liver tissues from the NCs, the liver tissues from the CSHB patients exhibited a significantly higher ratio of liver-infiltrating CD4(+) T cells to peripheral blood CD4(+) T-cell subsets (P = 0.001), and significantly lower ratios of liver-infiltrating NKT cells and B cells to the peripheral blood NKT-cells and B cells (P = 0.029 and P = 0.001 respectively).
Conclusion: The abundant infiltrating immune active cells, especially the CD4(+) T cells, CD8(+) T cells, and NK cells, may be the causal factors that drive the progressive development of CSHB.