title: Selective loss of innate CD4(+) V alpha 24 natural killer T cells in human immunodeficiency virus infection.
abstract: 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(+) 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.
authors.affiliation: Gladstone Institute of Virology and Immunology, University of California, San Francisco, California 94141, USA.
authors.forename: Johan K
authors.initials: JK
authors.lastname: Sandberg
authors.forename: Noam M
authors.initials: NM
authors.lastname: Fast
authors.forename: Emil H
authors.initials: EH
authors.lastname: Palacios
authors.forename: Glenn
authors.initials: G
authors.lastname: Fennelly
authors.forename: Joanna
authors.initials: J
authors.lastname: Dobroszycki
authors.forename: Paul
authors.initials: P
authors.lastname: Palumbo
authors.forename: Andrew
authors.initials: A
authors.lastname: Wiznia
authors.forename: Robert M
authors.initials: RM
authors.lastname: Grant
authors.forename: Nina
authors.initials: N
authors.lastname: Bhardwaj
authors.forename: Michael G
authors.initials: MG
authors.lastname: Rosenberg
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Nixon
mesh_terms: D000328:Adult; D000954:Antigens, Surface / Q000378:metabolism; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D002478:Cells, Cultured; D002648:Child; D015658:HIV Infections / Q000276:immunology* / Q000503:physiopathology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D019041:L-Selectin / Q000378:metabolism; D037181:Lectins, C-Type; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D055651:NK Cell Lectin-Like Receptor Subfamily B; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism*; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology
chemical_list: D000954:Antigens, Surface; C527203:KLRB1 protein, human; D037181:Lectins, C-Type; D016169:Lymphocyte Function-Associated Antigen-1; D055651:NK Cell Lectin-Like Receptor Subfamily B; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016201:Receptors, Lymphocyte Homing; D019041:L-Selectin