{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T02:39:55Z","timestamp":1789871995311,"version":"4.0.1"},"reference-count":25,"publisher":"American Society of Hematology","issue":"11","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2003,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>CD4, the primary receptor for entry of HIV, is known to be expressed on T cells and monocytes\/macrophages; healthy natural killer (NK) lymphocytes; in vitro human herpesvirus 6 (HHV6)\u2013infected CD8+, NK, and \u03b3\u03b4 T lymphocytes; CD34+ progenitor cells; and a subset of eosinophils and basophils. We here report the unconventional expression of CD4 at the surface of peripheral blood neutrophils derived from 4 of 51 (7.8%) HIV-1\u2013infected and 3 of 25 (12%) uninfected donors, with similar frequency within the 2 groups. The percentage of CD4+ neutrophils ranged from 39% to 97% of the total neutrophil population. Both surface and cytoplasmic forms of CD4 were present in neutrophils. Quantitative RNA polymerase chain reaction (PCR) revealed that neutrophils contain levels of CD4 mRNA comparable to those of peripheral blood mononuclear cells derived from the same donor. The conformation of CD4 expressed at the surface of neutrophils was similar to that of CD4 expressed on T lymphocytes as determined by the binding of monoclonal antibodies specific for conformational epitopes and the binding of recombinant HIV-1 gp120. Thus, our data provide evidence that neutrophils express endogenous CD4 and bind HIV. Owing to their abundance in peripheral blood, CD4+ neutrophils may influence significantly the biodistribution of HIV delivering it to sites of inflammation or to additional tissue reservoirs.<\/jats:p>","DOI":"10.1182\/blood-2002-10-3056","type":"journal-article","created":{"date-parts":[[2003,5,20]],"date-time":"2003-05-20T01:21:48Z","timestamp":1053393708000},"page":"4452-4456","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":55,"title":["Expression of CD4 on human peripheral blood neutrophils"],"prefix":"10.1182","volume":"101","author":[{"given":"Priscilla","family":"Biswas","sequence":"first","affiliation":[{"name":"From the Laboratory of Clinical Immunology, San Raffaele Scientific Institute, Milan, Italy; Clinic of Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy; Unit of Human Virology, San Raffaele Scientific Institute, Milan, Italy; Microscopy Service, San Raffaele Scientific Institute, Milan, Italy; Mario Negri Institute for Pharmacologic Research, Milan, Italy; and Japan Immunoresearch Laboratories, Takasaki, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Mantelli","sequence":"additional","affiliation":[{"name":"From the Laboratory of Clinical Immunology, San Raffaele Scientific Institute, Milan, Italy; Clinic of Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy; Unit of Human Virology, San Raffaele Scientific Institute, Milan, Italy; Microscopy Service, San Raffaele Scientific Institute, Milan, Italy; Mario Negri Institute for Pharmacologic Research, Milan, Italy; and Japan Immunoresearch Laboratories, Takasaki, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Sica","sequence":"additional","affiliation":[{"name":"From the Laboratory of Clinical Immunology, San Raffaele Scientific Institute, Milan, Italy; Clinic of Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy; Unit of Human Virology, San Raffaele Scientific Institute, Milan, Italy; Microscopy Service, San Raffaele Scientific Institute, Milan, Italy; Mario Negri Institute for Pharmacologic Research, Milan, Italy; and Japan Immunoresearch Laboratories, Takasaki, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro","family":"Malnati","sequence":"additional","affiliation":[{"name":"From the Laboratory of Clinical Immunology, San Raffaele Scientific Institute, Milan, Italy; Clinic of Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy; Unit of Human Virology, San Raffaele Scientific Institute, Milan, Italy; Microscopy Service, San Raffaele Scientific Institute, Milan, Italy; Mario Negri Institute for Pharmacologic Research, Milan, Italy; and Japan Immunoresearch Laboratories, Takasaki, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Panzeri","sequence":"additional","affiliation":[{"name":"From the Laboratory of Clinical Immunology, San Raffaele Scientific Institute, Milan, Italy; Clinic of Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy; Unit of Human Virology, San Raffaele Scientific Institute, Milan, Italy; Microscopy Service, San Raffaele Scientific Institute, Milan, Italy; Mario Negri Institute for Pharmacologic Research, Milan, Italy; and Japan Immunoresearch Laboratories, Takasaki, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Saccani","sequence":"additional","affiliation":[{"name":"From the Laboratory of Clinical Immunology, San Raffaele Scientific Institute, Milan, Italy; Clinic of Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy; Unit of Human Virology, San Raffaele Scientific Institute, Milan, Italy; Microscopy Service, San Raffaele Scientific Institute, Milan, Italy; Mario Negri Institute for Pharmacologic Research, Milan, Italy; and Japan Immunoresearch Laboratories, Takasaki, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamid","family":"Hasson","sequence":"additional","affiliation":[{"name":"From the Laboratory of Clinical Immunology, San Raffaele Scientific Institute, Milan, Italy; Clinic of Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy; Unit of Human Virology, San Raffaele Scientific Institute, Milan, Italy; Microscopy Service, San Raffaele Scientific Institute, Milan, Italy; Mario Negri Institute for Pharmacologic Research, Milan, Italy; and Japan Immunoresearch Laboratories, Takasaki, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Vecchi","sequence":"additional","affiliation":[{"name":"From the Laboratory of Clinical Immunology, San Raffaele Scientific Institute, Milan, Italy; Clinic of Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy; Unit of Human Virology, San Raffaele Scientific Institute, Milan, Italy; Microscopy Service, San Raffaele Scientific Institute, Milan, Italy; Mario Negri Institute for Pharmacologic Research, Milan, Italy; and Japan Immunoresearch Laboratories, Takasaki, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abby","family":"Saniabadi","sequence":"additional","affiliation":[{"name":"From the Laboratory of Clinical Immunology, San Raffaele Scientific Institute, Milan, Italy; Clinic of Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy; Unit of Human Virology, San Raffaele Scientific Institute, Milan, Italy; Microscopy Service, San Raffaele Scientific Institute, Milan, Italy; Mario Negri Institute for Pharmacologic Research, Milan, Italy; and Japan Immunoresearch Laboratories, Takasaki, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Lusso","sequence":"additional","affiliation":[{"name":"From the Laboratory of Clinical Immunology, San Raffaele Scientific Institute, Milan, Italy; Clinic of Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy; Unit of Human Virology, San Raffaele Scientific Institute, Milan, Italy; Microscopy Service, San Raffaele Scientific Institute, Milan, Italy; Mario Negri Institute for Pharmacologic Research, Milan, Italy; and Japan Immunoresearch Laboratories, Takasaki, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriano","family":"Lazzarin","sequence":"additional","affiliation":[{"name":"From the Laboratory of Clinical Immunology, San Raffaele Scientific Institute, Milan, Italy; Clinic of Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy; Unit of Human Virology, San Raffaele Scientific Institute, Milan, Italy; Microscopy Service, San Raffaele Scientific Institute, Milan, Italy; Mario Negri Institute for Pharmacologic Research, Milan, Italy; and Japan Immunoresearch Laboratories, Takasaki, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Beretta","sequence":"additional","affiliation":[{"name":"From the Laboratory of Clinical Immunology, San Raffaele Scientific Institute, Milan, Italy; Clinic of Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy; Unit of Human Virology, San Raffaele Scientific Institute, Milan, Italy; Microscopy Service, San Raffaele Scientific Institute, Milan, Italy; Mario Negri Institute for Pharmacologic Research, Milan, Italy; and Japan Immunoresearch Laboratories, Takasaki, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"key":"2020021222021476600_REF1","doi-asserted-by":"crossref","unstructured":"Janeway CAJ. The role of CD4 in T-cell activation: accessory molecule or coreceptor? Immunol Today. 1989;10: 234-238.","DOI":"10.1016\/0167-5699(89)90260-0"},{"key":"2020021222021476600_REF2","doi-asserted-by":"crossref","unstructured":"Sattentau QJ, Weiss R. The CD4 antigen: physiological ligand and HIV receptor. Cell. 1988;52: 631-633.","DOI":"10.1016\/0092-8674(88)90397-2"},{"key":"2020021222021476600_REF3","doi-asserted-by":"crossref","unstructured":"Moore JP, Trkola A, Dragic T. Co-receptors for HIV-1 entry. Curr Opin Immunol. 1997;9: 551-562.","DOI":"10.1016\/S0952-7915(97)80110-0"},{"key":"2020021222021476600_REF4","doi-asserted-by":"crossref","unstructured":"Berger EA, Murphy PM, Farber JM. Chemokine receptors as HIV-1 coreceptors: roles in viral entry, tropism, and disease. Annu Rev Immunol. 1999;17: 657-700.","DOI":"10.1146\/annurev.immunol.17.1.657"},{"key":"2020021222021476600_REF5","doi-asserted-by":"crossref","unstructured":"Filion LG, Izaguirre CA, Garber CA, Huebsh L, Aye MT. Detection of surface and cytoplasmic CD4 on blood monocytes from normal and HIV-1 infected individuals. J Immunol Methods. 1990;135: 59-69.","DOI":"10.1016\/0022-1759(90)90256-U"},{"key":"2020021222021476600_REF6","doi-asserted-by":"crossref","unstructured":"Lucey DR, Dorsky DI, Nicholson-Weller A, Weller PF. Human eosinophils express CD4 protein and bind human immunodeficiency virus 1 gp120. J Exp Med. 1989;169: 327-332.","DOI":"10.1084\/jem.169.1.327"},{"key":"2020021222021476600_REF7","doi-asserted-by":"crossref","unstructured":"Zauli G, Furlini G, Vitale M, et al. A subset of human CD34+ hematopoietic progenitors express low levels of CD4, the high affinity receptor for human immunodeficiency virus-type 1. Blood. 1994;84: 1896-1905.","DOI":"10.1182\/blood.V84.6.1896.1896"},{"key":"2020021222021476600_REF8","doi-asserted-by":"crossref","unstructured":"Louache DR, Debili N, Marandin A, Coulombel L, Vainchenker W. Expression of CD4 by human hematopoietic progenitors. Blood. 1994;84: 3344-3355.","DOI":"10.1182\/blood.V84.10.3344.3344"},{"key":"2020021222021476600_REF9","doi-asserted-by":"crossref","unstructured":"Lusso P, De Maria A, Malnati M, et al. Induction of CD4 and susceptibility to HIV-1 infection in human CD8+ T lymphocytes by human herpesvirus 6. Nature. 1991;349: 533-535.","DOI":"10.1038\/349533a0"},{"key":"2020021222021476600_REF10","doi-asserted-by":"crossref","unstructured":"Lusso P, Malnati MS, Garzino-Demo A, Crowley RW, Long EO, Gallo RC. Infection of natural killer cells by human herpesvirus 6. Nature. 1993;362: 458-462.","DOI":"10.1038\/362458a0"},{"key":"2020021222021476600_REF11","doi-asserted-by":"crossref","unstructured":"Lusso P, Garzino-Demo A, Crowley RW, Malnati MS. Infection of gamma\/delta T lymphocytes by human herpesvirus 6: transcriptional induction of CD4 and susceptibility to HIV infection. J Exp Med. 1995;181: 1303-1310.","DOI":"10.1084\/jem.181.4.1303"},{"key":"2020021222021476600_REF12","doi-asserted-by":"crossref","unstructured":"Li Y, Li L, Wadley R, et al. Mast cells\/basophils in the peripheral blood of allergic individuals who are HIV-1 susceptible due to their surface expression of CD4 and the chemokine receptors CCR3, CCR5, CXCR4. Blood. 2001;97: 3484-3490.","DOI":"10.1182\/blood.V97.11.3484"},{"key":"2020021222021476600_REF13","doi-asserted-by":"crossref","unstructured":"Valentin A, Rosati M, Patenaude DJ, et al. Persistent HIV-1 infection of natural killer cells in patients receiving highly active antiretroviral therapy. Proc Natl Acad Sci U S A. 2002;99: 7015-7020.","DOI":"10.1073\/pnas.102672999"},{"key":"2020021222021476600_REF14","doi-asserted-by":"crossref","unstructured":"Biswas P, Smith CA, Goletti D, Hardy EC, Jackson RW, Fauci AS. Cross-linking of CD30 induces HIV expression of human immunodeficiency virus in chronically infected T cells. Immunity. 1995;2: 587-596.","DOI":"10.1016\/1074-7613(95)90003-9"},{"key":"2020021222021476600_REF15","doi-asserted-by":"crossref","unstructured":"Scarlatti G, Tresoldi E, Bjorndal A, et al. In vivo evolution of HIV-1 co-receptor usage and sensitivity to chemokine-mediated suppression. Nat Med. 1997;3: 1259-1265.","DOI":"10.1038\/nm1197-1259"},{"key":"2020021222021476600_REF16","doi-asserted-by":"crossref","unstructured":"Nair KS, Zingde S. Adhesion of neutrophils to fibronectin: role of the CD66 antigens. Cell Immunol. 2001;208: 96-106.","DOI":"10.1006\/cimm.2001.1772"},{"key":"2020021222021476600_REF17","doi-asserted-by":"crossref","unstructured":"Moore JP, Sattentau QJ, Klasse PJ, Burkly LC. A monoclonal antibody to CD4 domain 2 blocks soluble CD4-induced conformational changes in the envelope glycoproteins of human immunodeficiency virus type 1 (HIV-1) and HIV infection of CD4+ cells. J Virol. 1992;66: 4784-4793.","DOI":"10.1128\/JVI.66.8.4784-4793.1992"},{"key":"2020021222021476600_REF18","doi-asserted-by":"crossref","unstructured":"Corbeau P, Benkirane M, Weil R, et al. Ig CDR3like region of the CD4 molecule is involved in HIV-induced syncytia formation but not in viral entry. J Immunol. 1993;150: 290-301.","DOI":"10.4049\/jimmunol.150.1.290"},{"key":"2020021222021476600_REF19","unstructured":"Suzuki H. Analysis of CD4\/CD8 lineage committment by pronase treatment and reexpression assay. Methods Mol Biol. 2000;134: 63-68."},{"key":"2020021222021476600_REF20","doi-asserted-by":"crossref","unstructured":"Forster R, Kremmer E, Schubel A, et al. Intracellular and surface expression of the HIV-1 coreceptor CXCR4\/fusin on various leukocyte subsets: rapid internalization and recycling upon activation. J Immunol. 1998;160: 1522-1531.","DOI":"10.4049\/jimmunol.160.3.1522"},{"key":"2020021222021476600_REF21","doi-asserted-by":"crossref","unstructured":"Berger EA, Doms RW, Fenyo EM, et al. A new classification for HIV-1. Nature. 1998;391: 240.","DOI":"10.1038\/34571"},{"key":"2020021222021476600_REF22","doi-asserted-by":"crossref","unstructured":"Kaneda T, Murukami T, Hagiwara T, et al. Defective HIV-1 provirus found in peripheral T lymphocytes and granulocytes in an AIDS patient imply viral infection of progenitor cells. AIDS. 2001;15: 939-940.","DOI":"10.1097\/00002030-200105040-00017"},{"key":"2020021222021476600_REF23","doi-asserted-by":"crossref","unstructured":"Sallusto F, Lanzavecchia A, Mackay CR. Chemokines and chemokine receptors in T-cell priming and Th1\/Th2-mediated responses. Immunol Today. 1998;19: 568-574.","DOI":"10.1016\/S0167-5699(98)01346-2"},{"key":"2020021222021476600_REF24","doi-asserted-by":"crossref","unstructured":"Gerard C, Rollins BJ. 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