The immune system is an intricate and fascinating network of many different cell types and signaling molecules that work together to protect the human body against foreign pathogens.

T cells are responsible for regulating the immune response, and much like a motley crew, they possess diverse backgrounds due to exposure to many different pathogens. It is this diversity, in part, which makes them such powerful regulators of the immune system.

However, T cells are more of an orchestrated motley crew – they consist of a diverse and seemingly unstructured set of cells, which are involved in an incredibly intricate and organized dance between destruction of foreign bodies and preservation of host cells.

Let’s explore that dance a little further. When you are exposed to a foreign pathogen, influenza virus for example, an antigen presenting cell (APC) such as a dendritic cell, will process and present viral antigens to your naïve CD4+ helper T cells.

The presentation of antigen serves to activate the T cell and stimulate it to secrete various cytokines and express specialized cell surface receptors. The specialized cell surface markers and cytokines will activate macrophages to destroy influenza, stimulate B cells to produce influenza specific antibodies, as well as maintain a steady level of self-tolerance to avoid destruction of your own cells and tissues.

The many roles just described are performed by a number of different subsets of CD4+ T cells, described in the table below.

 

CD4+ T Cell Subtype Activation Cytokines Phenotype Cytokine Expression Primary Function
Naïve CD4+ T cell Activated by APCs CD45RA+
CCR7+
IL-2 Proliferation and differentiation into subsets
Th1
T helper type 1
IL-12
IFN-γ
CXCR3+ IFN-γ
TNF-α and β
Production of pro-inflammatory cytokines; cell-mediated immunity
Th2
T helper type 2
IL-4
IL-2
CRTH2+
CCR4+
IL-4, IL-5
IL-13, IL-15
Production of anti-inflammatory cytokines; promote allergic response; evoke strong antibody response
Th17
T helper type 17
TGF-β, IL-6, IL-21, IL-23 CCR6+
CD161+
IL-17, IL-21
IL-22, IL-26
Respond to bacteria, fungi, and viruses; Auto-immune diseases
Th22
T helper type 22
IL-6 CCR4+
CCR10+
IL-22 Mucosal immune response; inflammatory diseases; barrier defense
Th9
T helper type 9
TGF-β
IL-4
? IL-9
IL-10
Humoral immunity through B cell interactions; functions on many cell types including mast cells and other CD4+ T cells
TFH
Follicular helper T cells
IL-6
IL-21
CXCR5+
ICOS+
IL-4
IL-21
Antigen specific B cell immunity
nTreg
Natural regulatory T cells
TGF-β
IL-2
CD25+
FOXP3+
TGF-β
IL-10
Maintenance of self-tolerance

 

To add to the complexity, each pathogen has a different composition of antigens that could be presented to naïve T cells. This means there is not only a large number of CD4+ T cell subsets responsible for specific roles, but also subsets of these subsets which are responsible for managing any particular pathogen. In addition, some T cells are like transformers in that they are able to toggle between different subtypes, making them a force to be reckoned with, even in an extreme infection environment.

Naïve CD4+ T cells are activated by APCs to produce T helper (Th) cells, regulatory T cells (Tregs), and follicular helper T cells (TFH).

The Th cells can be Th1, Th2, Th9, Th17, or Th22 cells, depending upon the pathogen and types of cytokines present in the cellular microenvironment. They are responsible for responding to both intracellular as well as extracellular pathogens and have also been found to be involved in various diseases.

Tregs are responsible for maintaining self-tolerance so host cells remain safe from immune attack, while the follicular helper T cells (TFH) are responsible for helping B cells produce pathogen specific antibodies.

Each subset can be characterized by expression of various cell surface markers as well as the cytokines it produces.

The figure below illustrates different CD4+ T cell differentiation paths and their respective phenotypic differences. Cell surface markers are listed on the top half of each cell type and cytokine expression profile on the bottom half, annotated by an asterisk (*). The cytokines responsible for inducing each cell type are represented by an arrow pointing from the naïve cell to each respective effector CD4+ helper T cell subset.

 

CD4+ helper T cell subsets image

 

Lonza CD4+ T cells (2W-200) are a mixture of all the various subsets present in the donor at the time of blood draw. If you are interested in a particular T cell subset, you can use Lonza CD4+ T cells to isolate the subset via immunomagnetic separation or FACS (fluorescence-activated cell sorting).

Please contact Lonza Scientific Support for more information. In addition, if you have large volume needs, we may be able to do custom cell isolations through our Cells on Demand Service.