title: Modulation of TIM-3 expression on NK and T cell subsets in HIV immunological non-responders.
abstract: Highly active antiretroviral therapy (HAART) for the treatment of HIV infection sustains viral suppression and increases CD4(+) T cells in HIV patients. However, in 10-25% of subjects, known as immunological non-responders (INRs), HAART does not increase CD4 count. We investigated a potential role for galectin-9 and TIM-3 in INRs as galectin-9 and TIM-3 have been described to modulate NK and T cell function. PBMCs were isolated from healthy controls, HIV immunological responders (IRs, >350CD4(+) cells/mm(3)) and HIV INRs (<350CD4(+) cells/mm(3)) and TIM-3 and galectin-9 expressions on NK cell subsets and CD4(+) T cells were assessed. HIV INRs and HIV IRs showed increased galectin-9 expression on CD16(-)CD56(bright) and CD16(+)CD56(+) NK cells and CD4(+) T cells. Only HIV INRs showed a reduced frequency of TIM-3-expressing CD16(+)CD56(+), CD16(+)CD56(-) and CD4(+) cells, which correlated with low peripheral CD4 counts. These data suggest that TIM-3 expression may be characteristic for HIV INRs.
authors.affiliation: Division of Digestive Diseases and Nutrition, Rush University Medical Center, Chicago, IL, USA. Electronic address: sander_dekivit@rush.edu.
authors.forename: Sander
authors.initials: S
authors.lastname: de Kivit
authors.affiliation: Department of Immunology/Microbiology, Rush University Medical Center, Chicago, IL, USA.
authors.forename: Ludwijn J R
authors.initials: LJ
authors.lastname: Lempsink
authors.affiliation: Department of Immunology/Microbiology, Rush University Medical Center, Chicago, IL, USA.
authors.forename: Jill
authors.initials: J
authors.lastname: Plants
authors.affiliation: Department of Immunology/Microbiology, Rush University Medical Center, Chicago, IL, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Martinson
authors.affiliation: Division of Digestive Diseases and Nutrition, Rush University Medical Center, Chicago, IL, USA; Division of Pharmacology, Utrecht Institute Pharmaceutical Sciences, Faculty of Science, Utrecht University, The Netherlands.
authors.forename: Ali
authors.initials: A
authors.lastname: Keshavarzian
authors.affiliation: Department of Immunology/Microbiology, Rush University Medical Center, Chicago, IL, USA; Division of Pharmacology, Utrecht Institute Pharmaceutical Sciences, Faculty of Science, Utrecht University, The Netherlands.
authors.forename: Alan L
authors.initials: AL
authors.lastname: Landay
mesh_terms: D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D037161:Galectins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000276:immunology*; D000072597:Hepatitis A Virus Cellular Receptor 2; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged
chemical_list: D037161:Galectins; C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; C105032:LGALS9 protein, human; D008565:Membrane Proteins
keywords: CD4(+) T cell; Galectin-9; HIV; Immunological non-responders; NK cells; TIM-3