Selective Decrease in Circulating Vα24+Vβ11+ NKT Cells During HIV Type 1 Infection

Abstract

CD1d-restricted NKT cells express an invariant TCR and have been demonstrated to play an important regulatory role in a variety of immune responses. Invariant NKT cells down-regulate autoimmune responses by production of type 2 cytokines and can initiate antitumor and antimicrobial immune responses by production of type 1 cytokines. Although defects in the (invariant) Vα24+Vβ11+ NKT cell population have been observed in patients with cancer and autoimmune diseases, little is known regarding the protective role of Vα24+Vβ11+ NKT cells in human infectious disease. In a cross-sectional study in HIV-1-infected individuals, we found circulating numbers of Vα24+Vβ11+ NKT cells to be reduced, independent of CD4+ T cell counts, CD4:CD8 ratios, and viral load. Because a small minority of Vα24+Vβ11+ NKT cells of healthy donors expressed HIV-1 (co)receptors and the vast majority of Vα24+Vβ11+ NKT cells in HIV-1-infected individuals expressed the Fas receptor, the depletion was more likely due to Fas-mediated apoptosis than to preferential infection of Vα24+Vβ11+ NKT cells by HIV-1. A longitudinal cohort study, in which patients were analyzed before seroconversion and 1 and 5 years after seroconversion, demonstrated that a large proportion of the depletion occurred within the first year postseroconversion. In this longitudinal study no evidence was found to support an important role of Vα24+Vβ11+ NKT cells in determining the rate of progression during HIV-1 infection.

Development of innate CD4+α-chain variable gene segment 24 (Vα24) natural killer T cells in the early human fetal thymus is regulated by IL-7

“…Loss or dysfunction of these cells occurs in autoimmune conditions (6)(7)(8)10), cancer (9,11), and viral infections (16)(17)(18)42). Investigation of the pathways and sites for development and differentiation of human V␣24 NK T cells is, therefore, important both for the basic understanding of the biology of these cells and for potential therapeutic interventions to restore or improve V␣24 NK T cell function in certain diseases.…”

“…The primary role of CD1d-restricted NK T cells is thought to be the regulation of immune responses, and several reports (6-11) support a role for NK T cell dysfunction in the pathogenesis of autoimmune diseases and cancers, as well as in murine models of autoimmunity (12)(13)(14)(15). They are lost in HIV-1 infection in humans (16)(17)(18) and lymphocytic choriomeningitis virus infection in mice (19), and they can be activated to participate in defense against hepatitis B virus and cytomegalovirus in mice (20,21).…”

Dominant effector memory characteristics, capacity for dynamic adaptive expansion, and sex bias in the innate Vα24 NKT cell compartment

“…The role for NKT cells in the pathogenesis of infectious diseases is less clear. However, the CD4 + V § 24 NKT cells were recently found to be extremely sensitive to HIV infection [11,23,24], and the corresponding murine V § 14 NKT cells are lost during acute infection with lymphocytic choriomeningitis virus (LCMV) [25].…”

NKT cells: Friend or foe during viral infections?

“…Longitudinal analysis revealed that the iNKT-cell depletion occurs largely during the first year after seroconversion [21]. The plasma HIV-1 RNA concentration correlates negatively with the CD4 1 iNKT-cell frequency but not with the total iNKT-cell frequency [20,21].…”