Clinical Implications of Peripheral Mononuclear Cells

Introduction

Blood in the human body is composed of a variety of cells and fluid components (plasma) that act comprehensively to achieve the desired circulation function to provide the necessary oxygen and nutrients. One among these is the mononuclear cells available in peripheral circulation.

What Are Peripheral Mononuclear Cells?

As implied by their name, peripheral mononuclear cells are immune cells that contain a single nucleus within their cells. Such cells are a mixture of lymphocytes (T cells, B cells, and natural killer cells) and monocytes. This characteristic presence of singular nuclei differentiates the peripheral mononuclear cells from other granulocytes that generally possess multiple and lobed nuclei.

What Are the Functions of Peripheral Mononuclear Cells?

• The main function of these mononuclear cells is to optimize the body's immune function by responding to the presence of foreign agents or antigens. Thus, they are the main defenders of the body and are responsible for eliminating all kinds of abnormal cells (immune surveillance and memory).

• Presentation of the antigens is carried out by dendritic cells and monocytes. This helps in the activation of other peripheral mononuclear cells and the elimination of a particular antigen.

• Conferring immunity to an individual by producing antibodies is another important role of peripheral mononuclear cells.

• Certain subsets of peripheral mononuclear cells, such as monocytes and regulatory T cells (Tregs), are involved in tissue repair and regeneration.

• A balance is maintained between normal immune responses and autoimmunity due to the presence of such peripheral mononuclear cells.

How to Separate Peripheral Mononuclear Cells?

Separating peripheral mononuclear cells is important for optimal utilization of these cells for diagnosis, therapeutic, and prognostic purposes. Centrifuging the blood sample obtained using dense gradients is the preferred method. The most commonly used method involves layering the blood sample onto a density gradient medium, such as Ficoll-Paque or Lymphoprep, and centrifuging it. This will create a layer of peripheral mononuclear cells that can help in other clinical purposes.

What Are the Clinical Implications of Peripheral Mononuclear Cells?

• Diagnostic Uses: Peripheral blood mononuclear cells are valuable diagnostic tools because they represent systemic immune status and accessibility through blood sampling.

  • Viral infections like hepatitis, HIV, or cytomegalovirus can be identified. This can be done by detecting the presence of viral DNA/RNA and pathogen-specific markers. With progressing infection, there is an alteration in the cell counts and ratios.

  • In autoimmune disorders, peripheral blood mononuclear cell (PBMC) profiling assists in diagnosing diseases characterized by aberrant immune responses against self-antigens. The detection of autoantibodies or dysregulated T cell subsets in PBMCs is characteristic of conditions representing autoimmunity like systemic lupus erythematosus or multiple sclerosis.

  • Cancer diagnosis is made easier by detecting tumor-specific markers in such mononuclear cells. Circulating tumor cells (CTCs) within PBMC fractions are biomarkers for cancer progression and treatment response.

• Therapeutic Purposes: Recent advances have also made use of these efficient peripheral mononuclear cells for therapeutic uses. This was possible because peripheral mononuclear cells can be detected, isolated, and regenerated.

  • In cancer therapy, peripheral mononuclear cells are utilized in adoptive cell therapy to incorporate the immune system's ability to target and eliminate tumor cells. Effector cells (such as cytotoxic T lymphocytes or natural killer cells) are isolated from mononuclear cells, activated, expanded ex vivo, and then infused into the patient to enhance anti-tumor immune responses. Additionally, chimeric antigen receptor (CAR) T cell therapy involves genetically modifying PBMC-derived T cells to express tumor-specific CARs, enabling precise targeting of the tumor cells. This therapy is mainly used in leukemia and lymphoma.

  • PBMC-based therapies aim to restore immune tolerance and mitigate autoimmune responses in autoimmune disorders. Regulatory T cells (Tregs) derived from PBMCs are potent suppressors of immune activation and inflammation, making them attractive candidates for immunomodulatory treatments. Adoptive transfer of ex vivo expanded Tregs has been employed in studies preclinically and clinically for diseases like type 1 diabetes and graft-versus-host disease (after transplantation of an organ).

  • The regenerative capacity of the peripheral mononuclear cells is utilized by extracting platelet-rich plasma. This can help in cell growth, proliferation, and angiogenesis due to the presence of necessary cytokines. Thus, this method treats musculoskeletal injuries, chronic wounds, and dermatological conditions. The potential of peripheral mononuclear cells to differentiate is also being studied to treat cardiac and orthopedic injuries.

• Prognostic Uses: Peripheral mononuclear cells are also used as an indicator for the prognosis of a condition.

  • In cancer, peripheral mononuclear cells (PBMCs) offer prognostic value by reflecting the systemic immune response to tumor progression and treatment. Changes in PBMC subsets, such as alterations in T cell subsets (e.g., CD4+ and CD8+ cells) and other defense cells like monocytes, are associated with different stages of cancer and prognosis. For example, a high ratio of CD8+ cytotoxic T cells to regulatory T cells within PBMCs has been correlated with improved survival in various cancer types, indicating a more favorable anti-tumor immune response.

  • Also, several cytokines and chemokines can be assessed as PBMC-derived factors. This assessment helps to get an overall insight into tumor aggressiveness, metastatic potential, and response to cancer therapy.

  • Similar detection of the cell ratios and cytokines can also provide an overview of the progression of infectious diseases. This is particularly essential for chronic infectious diseases like AIDS caused by the human immunodeficiency virus.

  • Aberrant PBMC subsets, such as activated T cells, autoantibody-producing B cells, and pro-inflammatory cytokines, can help identify the progression of autoimmune disorders and acute flare-ups of such disorders.

This clearly shows that peripheral mononuclear cells are dynamic cells that can be used clinically for multiple reasons to achieve various objectives.

What Are the Limitations of Peripheral Mononuclear Cells?

• These immune cells' composition and activation stage can vary between blood and tissue compartments, limiting a diagnosis based solely on the analysis of peripheral mononuclear cells.

• Isolation and manipulation of these cells ex vivo can introduce artifacts or alter their phenotype and function. This can specifically hinder their usage for therapeutic purposes.

• These cells may only be used partially if handled properly during storing and processing.

• Sometimes, data interpretation can become very complicated due to various phenotypes among these cells.

Conclusion

Integrating peripheral mononuclear cell-based biomarkers, functional assays, and molecular signatures into clinical practice enhances risk stratification and can effectively help in adept treatment planning. The versatility of such a group of cells should be utilized to the maximum potential for the healthy living of mankind.