자연살해세포의 특성을 보유한 특이한 CD56+CD19dim 세포
Unusual CD56 + CD19 dim Cells with Natural Killer Cell Characteristics
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
배경: 자연살해세포는 선천면역의 중요한 구성 요소로, 직접적인 세포독성과 사이토카인 분비 역할을 한다. 자연살해세포는 주로CD56과 다른 표지자들의 발현에 따라서 구분되는, 면역표현형과기능이 다른 다양한 하위집단으로 이루어져 있다. 자연살해세포는 일반적으로 B세포 표지자인 CD19를 발현하지 않지만, 드물게CD56+CD19dim 자연살해세포의 존재가 보고된 바 있다. 하지만 이들의 특성과 기능은 충분히 규명되지 않았다. 방법: 저자들은 CD56+CD19dim 자연살해세포의 존재에 초점을 맞추어, 3년 동안의 말초혈액 림프구아형검사 데이터를 후향적으로분석하였다. 그리고, 선별된 환자들의 신선한 말초혈액 샘플을 이용하여, 심층적인 면역표현형 분석과 기능적 프로파일링을 시행했다. 결과: 그 결과, CD56+CD19dim 세포는 일부 자연살해세포 표지자에 대하여는 일반적인 자연살해세포와 유사하였지만, CD94, CD158b의 높은 발현과 NKp30의 낮은 발현 같은 고유한 발현 패턴을 보였다. CD19는 CD56+CD19dim 세포에서 유일하게 발현되는B세포 관련 표지자였다. Granzyme B, Perforin, CD107a, IFN-γ, 그리고 MIP-1β를 포함한 기능 검사에서는, 세포독성 및 사이토카인분비 능력에 있어 CD56+CD19dim 세포와 일반 자연살해세포 간에유의한 차이가 없었다. 1,011명의 환자 중 17명(1.68%)에서 시행한총 40회의 림프구아형검사에서 CD56+CD19dim 자연살해세포가 확인되었으며, 이들은 전체 림프구의 0.10–24.70% (IQR 1.40–4.70%, 중앙값 2.20%)를 차지했다. 결론: 결론적으로, CD56+CD19dim 세포는 고유한 표현형적 특성을가진 독특한 자연살해세포의 하위집단이다. CD56+CD19dim 세포로 인하여 드물게 림프구아형검사나 B세포 림프모구백혈병의 미세잔존질환 검사에서 오판독이 발생할 수 있고, 치료 결정에 영향을 미칠 수 있으므로, 해당 아형을 인지하고 주의를 기울일 필요가있다.
Abstract
Background: Natural killer (NK) cells are critical components of innate immunity, known for their roles in direct cytotoxicity and cytokine secretion. NK cells exhibit diverse subpopulations with distinct immunophenotypes and functions, characterized primarily by their expression of CD56, along with other markers. While NK cells typically do not express the B-cell marker CD19, rare instances of CD56+CD19dim NK cells have been reported, although their characteristics and functions remain largely unknown. Methods: We retrospectively analyzed peripheral blood lymphocyte subset data during a 3-year period, focusing on the occurrence of CD56+CD19dim NK cells. In-depth immunophenotyping and functional profiling were conducted on fresh peripheral blood samples from selected patients. Results: CD56+CD19dim cells shared several NK cell markers with conventional NK cells, but had unique expression patterns, such as higher levels of CD94 and CD158b and lower levels of NKp30. CD19 was the only B-cell-related marker expressed in CD59+CD19dim cells. Functional assays including granzyme B, perforin, CD107a, IFN-γ, and MIP-1β revealed no significant differences in cytotoxic or cytokine secretory capabilities between CD56+CD19dim and typical NK cells. From 1,011 patients, 17 (1.68%) were found to have CD56+CD19dim NK cells in a total of 40 lymphocyte subset studies. CD56+CD19dim cells accounted for 0.10–24.70% (interquartile range 1.40–4.70%, median 2.20%) of lymphocytes. Conclusions: CD56+CD19dim cells represent a distinct NK cell subpopulation with unique phenotypic characteristics. Their rare presence in patients may lead to misinterpretation in lymphocyte subset analysis or minimal residual disease analysis of B-lymphoblastic leukemia, and affect therapeutic decisions, highlighting the need for awareness.
참고문헌 (24)
- Gasteiger G, "Interactions between innate and adaptive lymphocytes", Nat Rev Immunol, 14, pp.631~639 (2014)
- Cianga VA, "Natural killer cell subpopulations and inhibitory receptor dynamics in myelodysplastic syndromes and acute myeloid leukemia", Front Immunol, 12, pp.665541~ (2021)
- Cooper MA, "The biology of human natural killer-cell subsets", Trends Immunol, 22, pp.633~640 (2001)
- Hayakawa Y, "CD27 dissects mature NK cells into two subsets with distinct responsiveness and migratory capacity", J Immunol, 176, pp.1517~1524 (2006)
- Horowitz A, "Genetic and environmental determinants of human NK cell diversity revealed by mass cytometry", Sci Transl Med, 5, pp.208ra145~ (2013)
- Yang C, "Heterogeneity of human bone marrow and blood natural killer cells defined by single-cell transcriptome", Nat Commun, 10, pp.3931~ (2019)
- Wang K, "CD19 : a biomarker for B cell development, lymphoma diagnosis and therapy", Exp Hematol Oncol, 1, pp.36~ (2012)
- Bradbury LE, "The CD19", CD21 signal transducing complex of human B lymphocytes includes the target of antiproliferative antibody-1 and Leu-13 molecules, 1992, pp.149, 2841~2850
- Karawajew L, "Minimal residual disease analysis by eight-color flow cytometry in relapsed childhood acute lymphoblastic leukemia", Haematologica, 100, pp.935~944 (2015)
- Sigmund AM, "Evaluating blinatumomab for the treatment of relapsed", refractory ALL : design, development, and place in therapy, 2020, pp.10, 7~20
- Abramson JS, "Anti-CD19 CAR T-cell therapy for B-cell non-Hodgkin lymphoma", Transfus Med Rev, 34, pp.29~33 (2020)
- Soma L, "Apparent CD19 expression by natural killer cells : a potential confounder for minimal residual disease detection by flow cytometry in B lymphoblastic leukemia", Cytometry B Clin Cytom, 88, pp.145~147 (2015)
- Korol C, "NK cells expressing the B cell antigen CD19 : expanding the phenotypical characterization and the potential consequences from misinterpretation of this subset population", Cytometry B Clin Cytom, 88, pp.358~360 (2015)
- Li W, "Normal or reactive minor cell populations in bone marrow and peripheral blood mimic minimal residual leukemia by flow cytometry", Cytometry B Clin Cytom, 100, pp.590~601 (2021)
- Lanier LL, "Functional and biochemical analysis of CD16 antigen on natural killer cells and granulocytes", J Immunol, 141, pp.3478~3485 (1988)
- Pende D, "Identification and molecular characterization of NKp30, a novel triggering receptor involved in natural cytotoxicity mediated by human natural killer cells", J Exp Med, 190, pp.1505~1516 (1999)
- Vitale M, "NKp44, a novel triggering surface molecule specifically expressed by activated natural killer cells, is involved in non-major histocompatibility complex-restricted tumor cell lysis", J Exp Med, 187, pp.2065~2072 (1998)
- Sivori S, "P46, a novel natural killer cell-specific surface molecule that mediates cell activation", J Exp Med, 186, pp.1129~1136 (1997)
- Chester C, "Natural killer cell immunomodulation : targeting activating, inhibitory, and co-stimulatory receptor signaling for cancer immunotherapy", Front Immunol, 6, pp.601~ (2015)
- Sivori S, "IL-21 induces both rapid maturation of human CD34+ cell precursors towards NK cells and acquisition of surface killer Ig-like receptors", Eur J Immunol, 33, pp.3439~3447 (2003)
- Mattiola I, "Priming of human resting NK cells by autologous M1 macrophages via the engagement of IL-1β, IFN-β, and IL-15 pathways", J Immunol, 195, pp.2818~2828 (2015)
- Valés-Gómez M, "Kinetics and peptide dependency of the binding of the inhibitory NK receptor CD94", NKG2-A and the activating receptor CD94, EMBO J, pp.1999, 18[DOI]
- Gunturi A, "The role of CD94", NKG2 in innate and adaptive immunity, 2004, pp.30, 29~34
- van Zelm MC, "An antibody-deficiency syndrome due to mutations in the CD19 gene", N Engl J Med, 354, pp.1901~1912 (2006)