CLL cell expressing CD8 antigen

CD8 Antigen Expression in CLL: Is It Just a Curiosity or a Key to Better Treatment?

Jordan Keane in Health & Wellness December 2025 • 5 min read.

"Exploring the role of CD8 antigen expression in chronic lymphocytic leukemia (CLL) and its potential impact on diagnosis and treatment strategies."

Chronic Lymphocytic Leukemia (CLL) is a type of cancer that affects the blood and bone marrow. It's characterized by the accumulation of abnormal lymphocytes, a type of white blood cell. Diagnosing and understanding CLL involves a range of tests, one of which is looking at the presence or absence of certain proteins, called antigens, on the surface of these cells. In a recent study published in Cytometry: Part B-Clinical Cytometry, researchers, including Jain et al. (2018), explored a peculiar case: CLL cells expressing the CD8 antigen. This finding has sparked debate and further investigation in the medical community.

The CD8 antigen is typically found on T cells, another type of lymphocyte involved in the immune response. Its presence on CLL B-cells is unusual and has been reported in only a small fraction of CLL cases worldwide. The initial observation of CD8 expression on CLL B-cells dates back several years, and since then, various studies have attempted to understand its significance. However, due to the rarity of these cases, drawing definitive conclusions has been challenging.

This article delves into the complexities surrounding CD8 antigen expression in CLL. We will explore the existing research, potential explanations for this phenomenon, and whether it holds any clinical relevance for diagnosis, prognosis, or treatment strategies. Understanding these nuances is crucial for healthcare professionals and individuals affected by CLL, as it may pave the way for more personalized and effective approaches to managing this condition.

The Rarity of CD8+ CLL: Why Is It So Uncommon?

The fact that CD8 antigen is only rarely expressed in CLL raises a fundamental question: Why is this phenomenon so uncommon? Several factors may contribute to this rarity. The most straightforward explanation is that the genetic or environmental conditions required for CD8 expression in CLL B-cells are simply infrequent. However, there's another possibility linked to the diagnostic approaches used in different healthcare settings.

International guidelines recommend using a lymphocyte screening tube—a flow cytometry panel containing markers for B-lymphocytes (CD19, CD20, kappa, lambda), T-lymphocytes (CD3, CD4, CD5, CD8, CD38, TCRyd), and NK-lymphocytes (CD56). However, due to financial constraints and time-saving considerations, some centers, particularly in low-income countries, may not use this screening tube as the initial diagnostic step. Instead, they may rely on a combination of automated complete blood counts and peripheral blood smear reviews.

Cost and Resource Limitations: Comprehensive flow cytometry panels can be expensive. Centers with limited resources may opt for more targeted initial tests.
B-Cell Focus: Given that mature B-cell neoplasms are far more prevalent than T- or NK-cell neoplasms, initial diagnostic panels often focus on B-cell markers, potentially overlooking CD8 expression on B-cells.
Sequential Testing: If the initial B-cell panel doesn't lead to a diagnosis, the panel may be expanded to include additional markers like CD8. However, this sequential approach might delay or even miss the detection of CD8+ CLL in some cases.

Therefore, the perceived rarity of CD8+ CLL could be, in part, due to variations in diagnostic practices and the sensitivity of initial screening methods. This highlights the importance of standardized diagnostic protocols to ensure accurate and consistent detection of this subtype of CLL.

The Road Ahead: Integrating CD8 into CLL Prognosis

While the role of CD8 in CLL remains under investigation, it underscores the importance of comprehensive immunophenotyping in CLL diagnosis and risk stratification. As research continues, integrating CD8 expression, alongside other prognostic markers like CD1d and CD49d, may refine risk assessment and guide personalized treatment decisions. Collaboration and data sharing across research centers will be crucial to gather sufficient data and fully elucidate the clinical significance of CD8+ CLL. Ultimately, a deeper understanding of this rare CLL subtype may reveal novel therapeutic targets and improve outcomes for affected individuals.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1002/cyto.b.21759, Alternate LINK

Title: Cd8 Antigen Expression In Chronic Lymphocytic Leukemia: Does It Have Any Relevant Meaning?

Subject: Cell Biology

Journal: Cytometry Part B: Clinical Cytometry

Publisher: Wiley

Authors: Daniel Mazza Matos

Published: 2018-12-26

Everything You Need To Know

What is the significance of finding CD8 antigen on Chronic Lymphocytic Leukemia (CLL) B-cells, and why is it considered unusual?

The presence of CD8 antigen on CLL B-cells is notable because CD8 is typically found on T cells, which are different types of lymphocytes involved in immune response. Finding CD8 on CLL B-cells is unusual because CLL is characterized by the proliferation of abnormal B-cells. This phenomenon has been reported in a small fraction of CLL cases, prompting investigations into its potential impact on disease progression, diagnosis, and treatment effectiveness. Its rarity makes it challenging to draw definitive conclusions, but its presence could offer insights into personalized medicine approaches for CLL.

Why is CD8+ CLL so uncommon, and what factors might contribute to its perceived rarity?

The rarity of CD8 antigen expression in CLL B-cells is likely due to a combination of biological and diagnostic factors. The genetic or environmental conditions required for CD8 expression in CLL B-cells might be infrequent. Additionally, variations in diagnostic practices, such as the use of comprehensive flow cytometry panels that include markers for T-lymphocytes (CD3, CD4, CD5, CD8, CD38, TCRyd), can impact the detection of CD8+ CLL. Some centers, especially those with limited resources, may prioritize B-cell markers (CD19, CD20, kappa, lambda) in initial diagnostic panels, potentially overlooking CD8 expression on B-cells. Sequential testing, where CD8 is only assessed if initial B-cell panels are inconclusive, can also delay or miss the diagnosis of CD8+ CLL.

How do cost and resource limitations affect the detection of CD8+ CLL in different healthcare settings?

Cost and resource limitations can significantly impact the detection of CD8+ CLL. Comprehensive flow cytometry panels, including those with markers for both B-cells and T-cells, can be expensive. Centers with limited resources may opt for more targeted initial tests focusing on B-cell markers (CD19, CD20, kappa, lambda) since mature B-cell neoplasms are more common. This focus can lead to the overlooking of CD8 antigen expression on B-cells, as CD8 is typically associated with T-cells. The use of sequential testing, where additional markers like CD8 are only assessed if the initial B-cell panel is inconclusive, can further delay or miss the detection of CD8+ CLL in some cases. This highlights the importance of standardized diagnostic protocols to ensure consistent detection across different healthcare settings.

What role does immunophenotyping play in CLL diagnosis and risk stratification, and how might CD8 expression be integrated into this process?

Immunophenotyping, which involves identifying and characterizing cells based on the antigens they express, is crucial in CLL diagnosis and risk stratification. Comprehensive immunophenotyping helps in accurately classifying CLL subtypes and assessing their potential behavior. Integrating CD8 antigen expression, alongside other prognostic markers like CD1d and CD49d, into immunophenotyping panels may refine risk assessment and guide personalized treatment decisions. Further research and data sharing across research centers are essential to fully understand the clinical significance of CD8+ CLL and its potential impact on prognosis and treatment strategies.

How can a deeper understanding of the CD8 antigen expression in CLL lead to improved treatment outcomes?

A deeper understanding of CD8 antigen expression in CLL has the potential to reveal novel therapeutic targets and improve outcomes for affected individuals. By thoroughly investigating the characteristics and clinical behavior of CD8+ CLL, researchers may identify unique vulnerabilities that can be exploited with targeted therapies. Integrating CD8 expression into risk stratification models can also help tailor treatment approaches to individual patients, ensuring that those with CD8+ CLL receive the most appropriate and effective interventions. Further research, data sharing, and collaboration are essential to fully elucidate the clinical significance of CD8+ CLL and translate this knowledge into improved treatment strategies.