CD57 Antibody

What is CD57 and what cellular populations express this marker?

CD57 is an oligosaccharide antigenic determinant present on various polypeptides, lipids, and chondroitin sulphate proteoglycans. Its function remains incompletely understood. CD57 is expressed on a subset of natural killer (NK) cells, NK T cells, and both CD4+ and CD8+ T-cells in late stages of differentiation. CD57 also marks neuroendocrine cells and certain tumors derived from these cells, including carcinoid tumors and medulloblastomas .

What are the major aliases and genetic identifiers for CD57?

CD57 is known by multiple scientific designations:

What is the physiological significance of CD57 expression on lymphocytes?

CD57 expression on T-cells is generally associated with terminal differentiation, indicating cells that have undergone extensive rounds of antigen-driven proliferation. CD57+ T-cells exhibit reduced proliferative capacity but retain high cytotoxic potential. In NK cells, CD57 expression correlates with enhanced cytotoxicity and effector functions, including memory-like features. The frequency of CD57-expressing cells increases during aging and chronic immune activation, serving as a biomarker for immunosenescence .

How does CD57 expression change during human aging?

CD57 expression follows a distinct pattern throughout the human lifespan:

This age-related increase in CD57+CD8+ T-cells is a component of the "immune risk profile" that predicts higher all-cause mortality in elderly individuals .

How does CD57 expression differ between various T-cell subsets?

CD57 expression varies significantly between different T-cell populations:

What is the relationship between CD57 and other senescence markers like KLRG1?

The interrelationship between CD57 and KLRG1 provides valuable insights into cellular senescence:

These findings suggest that using both markers in combination provides more precise identification of truly senescent cells than either marker alone .

What are the optimal protocols for flow cytometric analysis using CD57 antibodies?

For optimal flow cytometric analysis with CD57 antibodies:

• Use pre-titrated antibodies at approximately 5 μL (0.25-1.0 μg) per test

• A test should contain 10^5 to 10^8 cells in a final volume of 100 μL

• For tandem dyes like PE-Cyanine7, protect samples from light due to sensitivity to photo-induced oxidation

• Samples can be stored in IC Fixation Buffer (100 μL cell sample + 100 μL fixation buffer) for up to 3 days at 4°C in the dark

• For PE-conjugated antibodies, excitation is 488-561 nm with emission at 578 nm

• For PE-Cyanine7 conjugates, excitation is 488-561 nm with emission at 775 nm

• Both can be excited by blue, green, or yellow-green lasers

How should researchers interpret discrepancies between CD57 expression and functional data?

CD57 expression doesn't always directly correlate with functional status. Previous studies may have overestimated the cytotoxic potential of CD57+CD8+ T-cells by failing to simultaneously assess intracellular expression of cytotoxic molecules and surface expression of the degranulation marker CD107a. In HIV infection, CD57+ cells show variable resistance to apoptosis despite being proliferation-incompetent. Therefore, researchers should employ multiple functional readouts alongside CD57 expression for comprehensive characterization .

What considerations should be made when designing multicolor flow cytometry panels including CD57?

When designing multicolor panels:

• Consider spectral overlap between fluorophores

• Account for different expression levels - CD57 may be expressed at variable levels on different cell subsets

• Include appropriate markers to identify specific cell populations (e.g., CD3, CD4, CD8, NK markers)

• Consider adding functional markers like CD107a (degranulation), granzymes, or perforin when assessing cytotoxic potential

• Include additional differentiation/exhaustion markers (CD27, CD28, KLRG1, PD-1) for comprehensive phenotyping

• Always use appropriate compensation controls, especially critical for tandem dyes

How is CD57 expression altered in chronic infections, and what are the functional implications?

CD57+CD8+ T-cells accumulate during chronic infections including:

These cells may provide effective protection through cytotoxic functions but may also limit immune repertoire diversity and contribute to immunopathology .

What is the significance of CD57 expression in cancer research?

CD57 has several applications in cancer research:

• Diagnostic utility: CD57 antibodies can help separate type B3 thymoma from thymic carcinoma when used with other markers like GLUT1, CD5, and CEA

• Tumor characterization: CD57 stains neuroendocrine cells and their derived tumors, including carcinoid tumors and medulloblastomas

• Prognostic indicator: Frequencies of CD57-expressing cells in blood and tissues correlate with clinical prognosis in various cancers

• T-cell phenotyping: Increased frequencies of CD57+CD4+ T-cells have been detected in patients with Hodgkin's lymphoma, chronic lymphocytic leukemia, and chronic leukemia of B-cell origin

These CD57+CD4+ T-cells display a typical Th1 cytokine profile upon TCR stimulation while retaining IL-2 secretion capability .

How do CD57+ NK cells differ functionally from CD57- NK cells?

CD57+ NK cells exhibit distinct functional properties:

• Enhanced cytotoxic potential compared to CD57- counterparts

• Display memory-like features, responding more robustly to secondary challenges

• May show altered cytokine production profiles

• Frequencies correlate with clinical outcomes in various diseases

• Represent a more terminally differentiated NK subset

Functional modulation of mature CD57+ NK cells may represent innovative strategies for protection against human immunological aging and/or various chronic diseases .

What are current limitations in understanding CD57 function, and how might these be addressed?

Several knowledge gaps exist in CD57 biology:

• The precise molecular function of CD57 remains poorly understood

• The relationship between CD57 expression, HCMV infection, TCR repertoire, and human physiological aging is incompletely characterized

• It's unclear whether CD57 represents a senescence marker in γδ T-cells as it does in αβ T-cells

• Functional differences between senescent and exhausted T-cells are likely context-dependent

To address these limitations, researchers should design comprehensive experiments that simultaneously assess multiple markers, perform functional assays, and conduct longitudinal studies across diverse populations .

How can researchers distinguish between CD57-mediated effects and other coincident phenotypic changes?

To distinguish CD57-specific effects:

• Use multiparameter approaches combining CD57 with other differentiation/exhaustion markers (CD27, CD28, CD45RA, CCR7, KLRG1, PD-1)

• Perform cell sorting of CD57+ and CD57- populations within the same differentiation stage for comparative functional analysis

• Consider genetic approaches to modulate CD57 expression

• Assess multiple functional parameters simultaneously (proliferation, cytotoxicity, cytokine production)

• Compare results across different disease settings and age groups

• Incorporate single-cell analysis techniques to account for heterogeneity within CD57+ populations

What are the recommended immunohistochemical protocols for CD57 detection in tissue samples?

For immunohistochemical detection:

• Use monoclonal antibodies like NK-1 clone for formalin-fixed, paraffin-embedded tissue sections

• The antibody should be supplied as purified immunoglobulin with <0.1% sodium azide as preservative

• Optimal dilutions should be determined and verified according to the detection system used

• Recommended positive controls include spleen and tonsil tissues

• The antibody is intended for qualitative immunohistochemistry with normal and neoplastic tissue sections viewed by light microscopy

• When combined with other markers (GLUT1, CD5, CEA), CD57 can help differentiate between type B3 thymoma and thymic carcinoma