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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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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\u2009+\u2009population 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\u2009+\u2009T effect by upregulating the expression of BAFFR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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\u2009+\u2009T effect.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s10020-025-01286-3","type":"journal-article","created":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T01:13:35Z","timestamp":1750382015000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Effect of anti-CD4 mAb induced by inhibiting B cell disorder on immune reconstruction of HIV-infected immunological non-responders"],"prefix":"10.1186","volume":"31","author":[{"given":"Yi","family":"Ouyang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panpan","family":"Yi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Da","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,20]]},"reference":[{"key":"1286_CR1","first-page":"207","volume":"21","author":"SM Bagheri Yazdi","year":"2022","unstructured":"Bagheri Yazdi SM, Shahsavandi S, Fotouhi F, Tebianian M, Ebrahimi MM. 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