Selective Loss of Innate CD4 super(+) V alpha 24 Natural Killer T Cells in Human Immunodeficiency Virus Infection

• Published in: Journal of virology 2002-08, Vol.76 (15), p.7528-7534
• Main Authors: Sandberg, J K, Fast, N M, Palacios, E H, Fennelly, G, Dobroszycki, J, Palumbo, P, Wiznia, A, Grant, R M, Bhardwaj, N, Rosenberg, M G, Nixon, D F
• Format: Article
• Language: English
• ISSN: 0022-538X
• DOI: 10.1128/JVI.76.15.7528-7534.2002

V alpha 24 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 V alpha 24 NKT cells can be subdivided into CD4 super(+) or CD4 super(-) subsets that differ in their expression of the homing receptors CD62L and CD11a. Furthermore, both CD4 super(+) and CD4 super(-) 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 super(+) T-cell depletion. The number of CD4 super(+) NKT cells is inversely correlated with HIV load, indicating depletion of this subset. In contrast, CD4 super(-) NKT-cell numbers are unaffected in subjects with high viral loads. HIV infection experiments in vitro show preferential depletion of CD4 super(+) NKT cells relative to regular CD4 super(+) T cells, in particular with virus that uses the CCR5 coreceptor. Thus, HIV infection causes a selective loss of CD4 super(+) lymph node homing (CD62L super(+)) NKT cells, with consequent skewing of the NKT-cell compartment to a predominantly CD4 super(-) CD62L super(-) phenotype. These data indicate that the key immunoregulatory NKT-cell compartment is compromised in HIV-1-infected patients.