Selective loss of innate CD4+ Vα24 natural killer T cells in human immunodeficiency virus infection

Johan K. Sandberg, Noam M. Fast, Emil H. Palacios, Glenn Fennelly, Joanna Dobroszycki, Paul Palumbo, Andrew Wiznia, Robert M. Grant, Nina Bhardwaj, Michael G. Rosenberg, Douglas F. Nixon

Research output: Contribution to journalArticlepeer-review

137 Scopus citations

Abstract

Vα24 natural killer T (NKT) cells are innate immune cells involved in regulation of immune tolerance, autoimmunity, and tumor immunity. However, the effect of human immunodeficiency virus type 1 (HIV-1) infection on these cells is unknown. Here, we report that the Vα24 NKT cells can be subdivided into CD4+ or CD4- subsets that differ in their expression of the homing receptors CD62L and CD11a. Furthermore, both CD4+ and CD4- NKT cells frequently express both CXCR4 and CCR5 HIV coreceptors. We find that the numbers of NKT cells are reduced in HIV-infected subjects with uncontrolled viremia and marked CD4+ T-cell depletion. The number of CD4+ NKT cells is inversely correlated with HIV load, indicating depletion of this subset. In contrast, CD4- NKT-cell numbers are unaffected in subjects with high viral loads. HIV infection experiments in vitro show preferential depletion of CD4+ NKT cells relative to regular CD4+ T cells, in particular with virus that uses the CCR5 coreceptor. Thus, HIV infection causes a selective loss of CD4+ lymph node homing (CD62L+) NKT cells, with consequent skewing of the NKT-cell compartment to a predominantly CD4- CD62L- phenotype. These data indicate that the key immunoregulatory NKT-cell compartment is compromised in HIV-1-infected patients.

Original languageEnglish
Pages (from-to)7528-7534
Number of pages7
JournalJournal of Virology
Volume76
Issue number15
DOIs
StatePublished - 2002
Externally publishedYes

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