Effect of anti-CD4 mAb induced by inhibiting B cell disorder on immune reconstruction of HIV-infected immunological non-responders.

BACKGROUND

In persons living with HIV, antiretroviral therapy (ART) reduces HIV RNA in their plasma and increases CD4 + T lymphocytes, thus restoring their immune function and reducing mortality rates.

METHODS

The heavy and light chains of B cell receptor (BCR) were amplified, sequenced, analyzed, and determined to be anti-CD4 mAb. The cytotoxicity of NK cells mediated by the anti-CD4 mAb was assessed using CCK-8, flow cytometry, ELISA, and western blotting. Detecting the viability/regulation of CD4 cells involved inhibiting the attachment of autoantibodies against CD4 to crucial receptors and detecting the inhibition of key molecules in B cells to produce anti-CD4 mAb in patients with immune non-responders (INR). Furthermore, through Phage Random Peptide Library Screening, we discovered that the AAPMFHSSVQLP-CD4 peptide has an affinity for the anti-CD4 mAb.

RESULTS

Administering anti-CD4 mAb enhanced NK cytotoxicity. The simultaneous administration of anti-CD4 mAb alongside GST-CD4 alleviated the harmful impacts of anti-CD4 mAb on the CD3 + population in humanized mice, and HIV virus (p24). Individuals diagnosed with INR displayed abnormal B cell activity, particularly with elevated BAFFR expression and increased levels of anti-CD4 mAb. Nevertheless, suppression of BAFFR hindered B cell function and decreased the production of anti-CD4 mAb. In HIV-infected individuals, the dysregulation of B-cells led to the production of anti-CD4 mAb, which in turn facilitated NK cell cytotoxicity and the CD4 + T effect by upregulating the expression of BAFFR.

CONCLUSION

The dysregulation of B-cells in person living with HIV increased the production of anti-CD4 mAb, which in turn promoted NK cell cytotoxicity and the CD4 + T effect.