The Journal of Experimental Medicine
Janeway's Immunobiology 7th Edition
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Published 1 April 2002. doi:10.1084/jem.20011712
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© Rockefeller University Press, 0022-1007/2002/4/869/ $5.00
The Journal of Experimental Medicine, Volume 195, Number 7, April 1, 2002 869-879

Original Article

 CD1d-restricted Human Natural Killer T Cells Are Highly Susceptible to Human Immunodeficiency Virus 1 Infection

Alison Motsinger1, David W. Haas1,2, Aleksandar K. Stanic1, Luc Van Kaer1,3, Sebastian Joyce1 and Derya Unutmaz1

1 Department of Microbiology and Immunology, Vanderbilt University Medical School, Nashville, TN 37232
2 Department of Medicine, Vanderbilt University Medical School, Nashville, TN 37232
3 Howard Hughes Medical Institute, Vanderbilt University Medical School, Nashville, TN 37232

Address correspondence to Derya Unutmaz, Department of Microbiology and Immunology, Vanderbilt University Medical School, 21st Ave. South, Medical Center North, Rm. AA-5216, Nashville, TN 37232-2363. Phone: 615-322 1435; Fax: 615-343 7392; E-mail: Derya.unutmaz{at}mcmail.vanderbilt.edu

Human natural killer (NK) T cells are unique T lymphocytes that express an invariant T cell receptor (TCR) V{alpha}24-Vß11 and have been implicated to play a role in various diseases. A subset of NKT cells express CD4 and hence are potential targets for human immunodeficiency virus (HIV)-1 infection. We demonstrate that both resting and activated human V{alpha}24+ T cells express high levels of the HIV-1 coreceptors CCR5 and Bonzo (CXCR6), but low levels of CCR7, as compared with conventional T cells. Remarkably NKT cells activated with {alpha}-galactosylceramide ({alpha}-GalCer)-pulsed dendritic cells were profoundly more susceptible to infection with R5-tropic, but not X4-tropic, strains of HIV-1, compared with conventional CD4+ T cells. Furthermore, resting CD4+ NKT cells were also more susceptible to infection. After initial infection, HIV-1 rapidly replicated and depleted the CD4+ subset of NKT cells. In addition, peripheral blood NKT cells were markedly and selectively depleted in HIV-1 infected individuals. Although the mechanisms of this decline are not clear, low numbers or absence of NKT cells may affect the course of HIV-1 infection. Taken together, our findings indicate that CD4+ NKT cells are directly targeted by HIV-1 and may have a potential role during viral transmission and spread in vivo.

Key Words: HIV • NKT cell • chemokine receptors • CD1d tetramer • cytokines


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