NKT cell depletion in humans during early HIV infection.
Natural killer T (NKT) cells bridge across innate and adaptive immune responses and have an important role in chronic viral infections such as human immunodeficiency virus (HIV). NKT cells are depleted during chronic HIV infection, but the timing, drivers and implications of this NKT cell depletion are poorly understood. We studied human peripheral blood NKT cell levels, phenotype and function in 31 HIV-infected subjects not on antiretroviral treatment from a mean of 4 months to 2 years after HIV infection. We found that peripheral CD4(+) NKT cells were substantially depleted and dysfunctional by 4 months after HIV infection. The depletion of CD4(+) NKT cells was more marked than the depletion of total CD4(+) T cells. Further, the early depletion of NKT cells correlated with CD4(+) T-cell decline, but not HIV viral levels. Levels of activated CD4(+) T cells correlated with the loss of NKT cells. Our studies suggest that the early loss of NKT cells is associated with subsequent immune destruction during HIV infection.
Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria, Australia.
Caroline S
CS
Fernandez
1] Kirby Institute, University of New South Wales, Kensington, New South Wales, Australia [2] St Vincent's Centre for Applied Medical Research, Sydney, New South Wales, Australia.
Anthony D
AD
Kelleher
Taylor Square Private Clinic, Darlinghurst, New South Wales, Australia.
Robert
R
Finlayson
Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria, Australia.
Dale I
DI
Godfrey
Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria, Australia.
Stephen J
SJ
Kent
D000328:Adult; D018791:CD4 Lymphocyte Count; D016022:Case-Control Studies; D005260:Female; D005699:Galactosylceramides / Q000494:pharmacology; D015658:HIV Infections / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000378:metabolism; D055611:Natural Killer T-Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D010641:Phenotype; D017452:Receptors, IgG / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D005699:Galactosylceramides; D055651:NK Cell Lectin-Like Receptor Subfamily B; D017452:Receptors, IgG; C493154:alpha-galactosylceramide