TCR gamma delta+ and CD161+ thymocytes express HIV-1 in the SCID-hu mouse, potentially contributing to immune dysfunction in HIV infection.
The vast diversity of the T cell repertoire renders the adaptive immune response capable of recognizing a broad spectrum of potential antigenic peptides. However, certain T cell rearrangements are conserved for recognition of specific pathogens, as is the case for TCRgammadelta cells. In addition, an immunoregulatory class of T cells expressing the NK receptor protein 1A (CD161) responds to nonpeptide Ags presented on the MHC-like CD1d molecule. The effect of HIV-1 infection on these specialized T cells in the thymus was studied using the SCID-hu mouse model. We were able to identify CD161-expressing CD3(+) cells but not the CD1d-restricted invariant Valpha24/Vbeta11/CD161(+) NK T cells in the thymus. A subset of TCRgammadelta cells and CD161-expressing thymocytes express CD4, CXCR4, and CCR5 during development in the thymus and are susceptible to HIV-1 infection. TCRgammadelta thymocytes were productively infectable by both X4 and R5 virus, and thymic HIV-1 infection induced depletion of CD4(+) TCRgammadelta cells. Similarly, CD4(+)CD161(+) thymocytes were depleted by thymic HIV-1 infection, leading to enrichment of CD4(-)CD161(+) thymocytes. Furthermore, compared with the general CD4-negative thymocyte population, CD4(-)CD161(+) NK T thymocytes exhibited as much as a 27-fold lower frequency of virus-expressing cells. We conclude that HIV-1 infection and/or disruption of cells important in both innate and acquired immunity may contribute to the overall immune dysfunction seen in HIV-1 disease.
Gurney
Kevin B
KB
Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, School of Medicine, 90095, USA.
Yang
Otto O
OO
Wilson
S Brian
SB
Uittenbogaart
Christel H
CH
D000818:Animals; D000954:Antigens, Surface / Q000096:biosynthesis*; D017252:CD3 Complex / Q000378:metabolism; D015704:CD4 Antigens / Q000096:biosynthesis; D002469:Cell Separation; D002478:Cells, Cultured; D015658:HIV Infections / Q000235:genetics / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology; D037181:Lectins, C-Type / Q000096:biosynthesis*; D051379:Mice; D016513:Mice, SCID; D055651:NK Cell Lectin-Like Receptor Subfamily B; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000096:biosynthesis*; D015728:Receptors, HIV / Q000096:biosynthesis; D013045:Species Specificity; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology* / Q000821:virology*
D000954:Antigens, Surface; D017252:CD3 Complex; D015704:CD4 Antigens; C527203:KLRB1 protein, human; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D016692:Receptors, Antigen, T-Cell, gamma-delta; D015728:Receptors, HIV