Preferential Infection of CD4+Memory T Cells by Human Immunodeficiency Virus Type 1: Evidence for a Role in the Selective T-Cell Functional Defects Observed in Infected Individuals

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 87; no. 16; pp. 6058 - 6062
• Main Authors: Schnittman, Steven M., Lane, H. Clifford, Greenhouse, Jack, Justement, Jesse S., Baseler, Michael, Fauci, Anthony S.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01.08.1990; National Acad Sciences
• Subjects: AIDS/HIV; Antigens; Antigens, CD - analysis; B lymphocytes; Biological and medical sciences; CD4 Antigens - analysis; CD4 Antigens - immunology; Cell growth; Cell lines; Cell Transformation, Viral; Cells, Cultured; DNA, Viral - genetics; DNA, Viral - isolation & purification; Fundamental and applied biological sciences. Psychology; HIV; HIV 1; HIV Seropositivity; HIV-1 - genetics; HIV-1 - immunology; Humans; Immunologic Memory; Infections; Memory; Microbiology; Polymerase Chain Reaction; Reference Values; Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains; T lymphocytes; T-Lymphocytes - immunology; Virology; Virus; Infection; Flow cytometry; Immunological memory; HIV-1 virus; Retroviridae; Lentivirinae; Human immunodeficiency virus; Lymphocyte
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.87.16.6058

CD4+T cells of patients with AIDS exhibit a qualitative defect in their ability to respond to soluble antigen while their responses to mitogens remain normal. CD4+T cells can be broadly divided phenotypically into "naive" [CD45RA+(2H4+)] and "memory" [CD29+(4B4+) or CD45RO+(UCHL1+)] cell subpopulations, which represent distinct maturation stages. To determine the human immunodeficiency virus type 1 (HIV-1) infectability of memory and naive CD4+T-cell subsets in vitro and to determine the in vivo preference of HIV-1 in these subpopulations, we obtained highly purified CD4+T-cell subsets from normal and HIV-1-infected individuals and studied them by viral cultivation, quantitative polymerase chain reaction, and functional assays. Polymerase chain reaction studies demonstrated that the memory cell subset of CD4+T cells is preferentially infected (4-to 10-fold more than naive T cells) by HIV-1 in vitro, and these memory cells are the principal reservoir for HIV-1 within CD4+T cells obtained from infected individuals. Functional abnormalities attributable to CD4+T cells in HIV-infected individuals (failure to respond in vitro to soluble antigen or to anti-CD3 monoclonal antibodies) were shown to reside primarily within these memory cells. Thus, the present study suggests that the selective functional defects present in the memory CD4+T-cell subset of HIV-infected individuals may be a direct result of the preferential infection and consequently greater viral burden within these cells.