학술논문
Comparison of primary human cytotoxic T-cell and natural killer cell responses reveal similar molecular requirements for lytic granule exocytosis but differences in cytokine production.
Document Type
Article
Author
Chiang, Samuel C. C.; Theorell, Jakob; Entesarian, Miriam; Meeths, Marie; Mastafa, Monika; Al-Herz, Waleed; Frisk, Per; Gilmour, Kimberly C.; Ifversen, Marianne; Langenskiöld, Cecilia; Machaczka, Maciej; Naqvi, Ahmed; Payne, Jeanette; Perez-Martinez, Antonio; Sabel, Magnus; Unal, Ekrem; Unal, Sule; Winiarski, Jacek; Nordenskjöld, Magnus; Ljunggren, Hans-Gustaf
Source
Subject
*CYTOTOXIC T cells
*KILLER cells
*EXOCYTOSIS
*CYTOKINES
*GRANZYMES
*PHENOTYPES
*HEMATOPOIETIC growth factors
*
*
*
*
*
*
Language
ISSN
0006-4971
Abstract
Cytotoxic lymphocytes, encompassing cytotoxic T lymphocytes (CTL) and natural killer (NK) cells, kill pathogen-infected, neoplastic, or certain hematopoietic cells through release of perforin-containing lytic granules. Here, we first performed probability state modeling of differentiation and lytic granule markers on CD8+ T cells to enable the comparison of bona fide CTL with NK cells. Analysis identified CD57bright-expression as a reliable phenotype of granule marker-containing CTL. We then compared CD3+CD8+CD57bright CTL with NK cells. Healthy adult peripheral blood CD3+CD8+CD57bright CTL expressed more granzyme B but less perforin than CD3-CD56dim NK cells. Upon stimulation, such CTL degranulated more readily than other T cell subsets, but had a similar propensity to degranulate as NK cells. Remarkably, the CTL produced cytokines more rapidly and with greater frequency than NK cells. In patients with biallelic mutations in UNC13D, STX11, or STXBP2 associated with familial hemophagocytic lymphohistocytosis (FHL), CTL and NK cell degranulation was similarly impaired. Thus, cytotoxic lymphocyte subsets have similar requirements for Munc13-4, syntaxin-11, and Munc18-2 in lytic granule exocytosis. The present results provide a detailed comparison of human CD3+CD8+CD57bright CTL and NK cells, and suggest that analysis of CD57bright CTL-function may prove useful in the diagnosis of primary immunodeficiencies including FHL. [ABSTRACT FROM AUTHOR]