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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
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
Blood, Volume 121, No. 8, Year 2013
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Description
Cytotoxic lymphocytes, encompassing cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells, kill pathogen-infected, neoplastic, or certain hematopoietic cells through the release of perforin-containing lytic granules. In the present study, we first performed probability-state modeling of differentiation and lytic granule markers on CD8+ T cells to enable the comparison of bona fide CTLs with NK cells. Analysis identified CD57 bright expression as a reliable phenotype of granule marker-containing CTLs. We then compared CD3+CD8+CD57 bright CTLs with NK cells. Healthy adult peripheral blood CD3 +CD8+CD57bright CTLs expressed more granzyme B but less perforin than CD3-CD56dim NK cells. On stimulation, such CTLs degranulated more readily than other T-cell subsets, but had a propensity to degranulate that was similar to NK cells. Remarkably, the CTLs produced cytokines more rapidly and with greater frequency than NK cells. In patients with biallelic mutations in UNC13D, STX11, or STXBP2associated with familial hemophagocytic lymphohistiocytosis, CTL and NK cell degranulation were similarly impaired. Therefore, 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 CTLs and NK cells and suggest that analysis of CD57bright CTL function may prove useful in the diagnosis of primary immunodeficiencies including familial hemophagocytic lymphohistiocytosis. © 2013 by The American Society of Hematology.
Authors & Co-Authors
Chiang, Samuel Cern Cher
Sweden, Stockholm
Karolinska Institutet
Theorell, Jakob
Sweden, Stockholm
Karolinska Institutet
Entesarian, Miriam
Sweden, Stockholm
Karolinska Institutet
Sweden, Stockholm
Karolinska Universitetssjukhuset
Meeths, Marie
Sweden, Stockholm
Karolinska Institutet
Sweden, Stockholm
Karolinska Universitetssjukhuset
Mastafa, Monika
Sweden, Stockholm
Karolinska Institutet
Sweden, Stockholm
Karolinska Universitetssjukhuset
Al-Herz, Waleed
Kuwait, Kuwait City
Kuwait University
Frisk, Per
Sweden, Uppsala
Uppsala Universitet
Gilmour, Kimberly C.
United Kingdom, London
Great Ormond Street Hospital for Children Nhs Foundation Trust
Ifversen, Marianne R.S.
Denmark, Copenhagen
Rigshospitalet
Langenskiöld, Cecilia
Sweden, Gothenburg
Drottning Silvias Barnsjukhus
Machaczka, Maciej
Sweden, Stockholm
Karolinska Universitetssjukhuset
Naqvi, Ahmed
Pakistan, Karachi
The Aga Khan University
Canada, Toronto
Hospital for Sick Children University of Toronto
Payne, Jeanette
United Kingdom, Sheffield
Sheffield Children's Hospital
Peréz-Martínez, Antonio
Spain, Madrid
Hospital Infantil Universitario Niño Jesús
Sabel, Magnus
Sweden, Gothenburg
Drottning Silvias Barnsjukhus
Unal, Ekrem K.
Turkey, Kayseri
Erciyes Üniversitesi
Ünal, Şule
Turkey, Ankara
Hacettepe Üniversitesi
Winiarski, Jacek
Sweden, Stockholm
Karolinska Universitetssjukhuset
Nordenskjöld, Magnus
Sweden, Stockholm
Karolinska Universitetssjukhuset
Ljunggren, Hans Gustaf
Sweden, Stockholm
Karolinska Institutet
Henter, Jan Inge
Sweden, Stockholm
Karolinska Institutet
Bryceson, Yenan Troi
Sweden, Stockholm
Karolinska Institutet
Norway, Bergen
Universitetet I Bergen
Statistics
Citations: 22
Authors: 22
Affiliations: 14
Identifiers
Doi:
10.1182/blood-2012-07-442558
ISSN:
00064971