NKT cells contribute to the modulation of immune responses and are believed to be important in the pathogenesis of autoimmune and infectious diseases, as well as cancer. Variations in the composite NKT cytokine response may determine individual disease susceptibility or severity. Due to low frequencies in peripheral blood, knowledge of the breadth of ex vivo human NKT cell functions has been limited. To bridge this gap, we studied highly purified NKT cells from PBMC of healthy donors and assessed the production of 27 effector functions using sensitive Elispot and multiplex bead assays. We found the ex vivo human NKT cell response is predominantly comprised of the chemokines MIP1-α, and MIP1-β as well as the Th1 cytokines IFN-γ and TNF-α. Although lower in magnitude, there was also significant production of IL-2, IL-4, and perforin after mitogen stimulation. Surprisingly, little/no IL-5, IL-6, IL-10, or IL-13 was detected, and no subjects' NKT cells produced IL-17. Comparison of the NKT functional profiles between age-matched male and female subjects revealed similar IL-4 responses, but higher frequencies of cells producing IFN-γ and MIP1-α, from males. There were no gender differences in the circulating NKT subset distribution. These findings implicate chemokines as a major mechanism by which NKT cells control responses in humans. In addition, the panoply of Th2 and Th17 cytokine secretion by NKT cells from healthy donors may not be as pronounced as previously believed. NKT cells may therefore contribute to the gender bias found in many diseases.

A Comprehensive Ex Vivo Functional Analysis of Human NKT Cells Reveals Production of MIP1-alpha and MIP1-beta, a Lack of IL-17, and a Th1-Bias in Males / J.E. Snyder Cappione, C. Tincati, I.G. Eccles James, A.J. Cappione III, L.C. Ndhlovu, L.L. Koth, D.F. Nixon. - In: PLOS ONE. - ISSN 1932-6203. - 5:11(2010), pp. e15412.1-e15412.9. [10.1371/journal.pone.0015412]

A Comprehensive Ex Vivo Functional Analysis of Human NKT Cells Reveals Production of MIP1-alpha and MIP1-beta, a Lack of IL-17, and a Th1-Bias in Males

C. Tincati
Secondo
;
2010

Abstract

NKT cells contribute to the modulation of immune responses and are believed to be important in the pathogenesis of autoimmune and infectious diseases, as well as cancer. Variations in the composite NKT cytokine response may determine individual disease susceptibility or severity. Due to low frequencies in peripheral blood, knowledge of the breadth of ex vivo human NKT cell functions has been limited. To bridge this gap, we studied highly purified NKT cells from PBMC of healthy donors and assessed the production of 27 effector functions using sensitive Elispot and multiplex bead assays. We found the ex vivo human NKT cell response is predominantly comprised of the chemokines MIP1-α, and MIP1-β as well as the Th1 cytokines IFN-γ and TNF-α. Although lower in magnitude, there was also significant production of IL-2, IL-4, and perforin after mitogen stimulation. Surprisingly, little/no IL-5, IL-6, IL-10, or IL-13 was detected, and no subjects' NKT cells produced IL-17. Comparison of the NKT functional profiles between age-matched male and female subjects revealed similar IL-4 responses, but higher frequencies of cells producing IFN-γ and MIP1-α, from males. There were no gender differences in the circulating NKT subset distribution. These findings implicate chemokines as a major mechanism by which NKT cells control responses in humans. In addition, the panoply of Th2 and Th17 cytokine secretion by NKT cells from healthy donors may not be as pronounced as previously believed. NKT cells may therefore contribute to the gender bias found in many diseases.
killer T-cells; experimental autoimmune encephalomyelitis; nonobese diabetic mice; ROR-gamma-T; cutting edge; tumor immunosurveillance; protects mice; activation; infection; receptor
Settore MED/17 - Malattie Infettive
Settore MED/04 - Patologia Generale
Article (author)
File in questo prodotto:
File Dimensione Formato  
Snyder-Cappione PlosOne 2010.pdf

accesso aperto

Tipologia: Publisher's version/PDF
Dimensione 773.88 kB
Formato Adobe PDF
773.88 kB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/448503
Citazioni
  • ???jsp.display-item.citation.pmc??? 20
  • Scopus 34
  • ???jsp.display-item.citation.isi??? 32
social impact