Document Detail

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.
MedLine Citation:
PMID:  23287865     Owner:  NLM     Status:  Publisher    
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 CD57(bright)-expression as a reliable phenotype of granule marker-containing CTL. We then compared CD3(+)CD8(+)CD57(bright) CTL with NK cells. Healthy adult peripheral blood CD3(+)CD8(+)CD57(bright) CTL expressed more granzyme B but less perforin than CD3(-)CD56(dim) 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(+)CD57(bright) CTL and NK cells, and suggest that analysis of CD57(bright) CTL-function may prove useful in the diagnosis of primary immunodeficiencies including FHL.
Samuel C C Chiang; Jakob Theorell; Miriam Entesarian; Marie Meeths; Monika Mastafa; Waleed Al-Herz; Per Frisk; Kimberly C Gilmour; Marianne Ifversen; Cecilia Langenskiöld; Maciej Machaczka; Ahmed Naqvi; Jeanette Payne; Antonio Perez-Martinez; Magnus Sabel; Ekrem Unal; Sule Unal; Jacek Winiarski; Magnus Nordenskjöld; Hans-Gustaf Ljunggren; Jan-Inge Henter; Yenan T Bryceson
Related Documents :
17105875 - Stem cells to repair the broken heart: much ado about nothing?
16826795 - Stem cell therapy for ischemic heart disease: beginning or end of the road?
24136885 - Natural killer cell therapy and aerosol interleukin-2 for the treatment of osteosarcoma...
11169455 - Growth factor supplemented matrigel improves ectopic skeletal muscle formation--a cell ...
23170195 - New strategies for stem cell mobilization.
1087095 - Cellular interactions in the proliferative response of human circulating lymphocytes to...
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-2
Journal Detail:
Title:  Blood     Volume:  -     ISSN:  1528-0020     ISO Abbreviation:  Blood     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-4     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden;
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  The role of chromatin modifiers in normal and malignant hematopoiesis.
Next Document:  OBFC2A/RARA: a novel fusion gene in variant acute promyelocytic leukemia.