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Stimulation of human lymphocyte proliferation and CD40 antigen expression by phosphorothioate oligonucleotides
1Department of Infectious Diseases 105th Hospital, HeFei, People's Republic of China.
Abstract:
We have studied the proliferation and CD40 antigen expression of lymphocytes, and the cytotoxicity to monocytes, of antisense phosphorothioate oligodeoxynucleotides complementary to the SP II promoter of HBV mRNA (sequence I) and the X gene (sequence II) in patients with chronic hepatitis B. The oligo sequence I stimulated proliferation of both T and, to a lesser extent, B cells. The percentage of cells expressing CD40 in T and B cell co-cultures increased from 4.2% to 13.8% after oligo stimulation in patients, while it increased form 4.7% to 48.6% in healthy controls. The sense sequence (sequence III) of the X gene also enhanced the expression of CD40 antigen in patients with hepatitis B. The proportion of CD40 cells (26%) in a resting B-cell preparation from hepatitis B patients decreased to zero after a 5-day culture with sequence I, but IgG levels in the culture supernatant increased. The cytotoxic properties of monocytes were not influenced by the oligos. These findings indicate that antisense oligos against hepatitis B virus (HBV) have mitogenic effects on the proliferation of human lymphocytes in a non-specific manner and may activate T cells to express CD40 antigen.
Insights
Antisense oligonucleotides targeting hepatitis B virus (HBV) stimulated lymphocyte proliferation and CD40 antigen expression in chronic hepatitis B patients. These HBV-targeted oligos showed non-specific mitogenic effects on human lymphocytes.
Area of Science:
- Immunology
- Virology
- Molecular Biology
Background:
- Chronic hepatitis B (CHB) is a significant global health concern.
- Antisense oligonucleotides (ASOs) are investigated for their therapeutic potential against viral infections.
- Understanding the immunomodulatory effects of ASOs is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the effects of antisense phosphorothioate oligodeoxynucleotides targeting HBV mRNA SP II promoter and X gene on lymphocyte proliferation and CD40 antigen expression in CHB patients.
- To assess the impact of these ASOs on monocyte cytotoxicity.
Main Methods:
- Studied proliferation and CD40 antigen expression of lymphocytes (T and B cells) in CHB patients and healthy controls upon stimulation with HBV-targeted antisense oligos.
- Assessed monocyte cytotoxicity following oligo treatment.
- Analyzed changes in CD40-positive cells and IgG levels in cell cultures.
Main Results:
- Oligo sequence I (targeting HBV mRNA SP II promoter) stimulated T and B cell proliferation in CHB patients.
- CD40 antigen expression on lymphocytes increased significantly in CHB patients and healthy controls after oligo stimulation, with greater magnitude in controls.
- Sense sequence (sequence III) also enhanced CD40 expression in CHB patients.
- Monocyte cytotoxicity was not affected by the oligos.
- A decrease in CD40-positive B cells was observed with sequence I, accompanied by increased IgG levels.
Conclusions:
- Antisense oligos targeting HBV exhibit non-specific mitogenic effects on human lymphocyte proliferation.
- These oligos may activate T cells, leading to CD40 antigen expression.
- Further research is needed to elucidate the precise mechanisms and therapeutic implications of these immunomodulatory effects in CHB.