Productive HIV-1 infection is enriched in CD4(-)CD8(-) double negative (DN) T cells at pleural sites of dual infection with HIV and Mycobacterium tuberculosis.
A higher human immunodeficiency virus 1 (HIV-1) viral load at pleural sites infected with Mycobacterium tuberculosis (MTB) than in peripheral blood has been documented. However, the cellular source of productive HIV infection in HIV-1/MTB-coinfected pleural fluid mononuclear cells (PFMCs) remains unclear. In this study, we observed significant quantities of HIV-1 p24(+) lymphocytes in PFMCs, but not in peripheral blood mononuclear cells (PBMCs). HIV-1 p24(+) lymphocytes were mostly enriched in DN T cells. Intracellular CD4 expression was detectable in HIV-1 p24(+) DN T cells. HIV-1 p24(+) DN T cells showed lower surface expression of human leukocyte antigen (HLA)-ABC and tetherin than did HIV-1 p24(+) CD4 T cells. Upon in vitro infection of PFMC CD4 T cells from TB mono-infected subjects, Nef- and/or Vpu-deleted HIV mutants showed lower generation of HIV-1 p24(+) DN T cells than the wild-type virus. These data indicate that productively HIV-1-infected DN T cells, generated through down-modulation of surface CD4, likely by HIV-1 Nef and Vpu, are the predominant source of HIV-1 at pleural sites of HIV/MTB coinfection.
Division of Infectious Diseases, Department of Medicine, BRB 10W, Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH, 44106-4984, USA. qxm8@case.edu.
Qinglai
Q
Meng
Division of Infectious Diseases, Department of Medicine, BRB 10W, Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH, 44106-4984, USA.|Veterans Affairs Medical Center, Cleveland, OH, USA.
David H
DH
Canaday
Department of Molecular Biology and Microbiology, Case Western Reserve University, Cleveland, OH, USA.
David J
DJ
McDonald
Division of Infectious Diseases, Department of Medicine, BRB 10W, Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH, 44106-4984, USA.|Makerere University, Kampala, Uganda.
Harriet
H
Mayanja-Kizza
Joint Clinical Research Center, Kampala, Uganda.
Joy
J
Baseke
Division of Infectious Diseases, Department of Medicine, BRB 10W, Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH, 44106-4984, USA. zxt2@case.edu.|Veterans Affairs Medical Center, Cleveland, OH, USA. zxt2@case.edu.
Zahra
http://orcid.org/0000-0002-2060-0674
Z
Toossi
D000328:Adult; D060085:Coinfection / Q000276:immunology* / Q000382:microbiology / Q000821:virology; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000382:microbiology / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008297:Male; D009169:Mycobacterium tuberculosis / Q000502:physiology*; D010994:Pleura / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology* / Q000382:microbiology; D055815:Young Adult
Double-negative T cell; HIV-1; PFMC; T cell; Tuberculosis