Selective loss of innate CD4(+) V alpha 24 natural killer T cells in human immunodeficiency virus infection.
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.
Sandberg
Johan K
JK
Gladstone Institute of Virology and Immunology, University of California, San Francisco, California 94141, USA.
Fast
Noam M
NM
Palacios
Emil H
EH
Fennelly
Glenn
G
Dobroszycki
Joanna
J
Palumbo
Paul
P
Wiznia
Andrew
A
Grant
Robert M
RM
Bhardwaj
Nina
N
Rosenberg
Michael G
MG
Nixon
Douglas F
DF
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
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