Lifespan of helper T cell

Lifespan of helper T cell

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CD4+ cells or helper T cells are produced in Thymus. How long these cells live? For example, RBC live for 3-4 months.

I will respond with a "story-like" approach. You may already know some info but I want to be sure I can help you fully understand!

Unlike RBC, you are born with all the CD4+ (or Th, as I refer to them) you will ever need in your lifetime in the primary organs of the immune system -- they are already specialized and ready to be used, and this has taken place in the thymus. On the other hand, RBC get renewed through erythropoiesis every ~120 days.

In utero, the thymus and bone marrow (primary organs) now supply secondary organs (lymph nodes, the spleen, the MALT) with the various cells they've made (B&T). However, only 5% leave the thymus, as 95% are recognized as "anti-self" and are killed. So this would be the first "killing" of Th cells. B cells live in the peripheral layer, while T cells live in the deep lymphoid tissue and the lymphoid dullet.

The dendritic cell will "wander" into the lymph node, carrying the fragment of antigen presentation on the MHC class 2 molecule-Dendritic cell resides between the B cell area and the T cell area. Now, the first specific thing occurs in the immune response, when the T cell receptor attaches to the antigen and tells cell says to make antibodies.

Now -- as of here, we have a lot of Th (and B) cells doing nothing while the antibody is being produced. Some of the Th will be killed, while some will serve as "memory Th cells" so that the next time such an antigen is present in your body, the response will be quicker. At this point, it's hard to distinguish which Th cells are dividing, and which are dying. The average lifespan has been reported to be >17 years. Source:

I hope I have been able to help.

The life (and death) of CD4+ CD28(null) T cells in inflammatory diseases

Inflammation contributes to the development and perpetuation of several disorders and T lymphocytes orchestrate the inflammatory immune response. Although the role of T cells in inflammation is widely recognized, specific therapies that tackle inflammatory networks in disease are yet to be developed. CD4(+) CD28(null) T cells are a unique subset of helper T lymphocytes that recently shot back into the limelight as potential catalysts of inflammation in several inflammatory disorders such as autoimmunity, atherosclerosis and chronic viral infections. In contrast to conventional helper T cells, CD4(+) CD28(null) T cells have an inbuilt ability to release inflammatory cytokines and cytotoxic molecules that can damage tissues and amplify inflammatory pathways. It comes as no surprise that patients who have high numbers of these cells have more severe disease and poor prognosis. In this review, I provide an overview on the latest advances in the biology of CD4(+) CD28(null) T cells. Understanding the complex functions and dynamics of CD4(+) CD28(null) T cells may open new avenues for therapeutic intervention to prevent progression of inflammatory diseases.

Keywords: CD4+CD28null T lymphocytes apoptosis atherosclerosis autoimmunity co-stimulation helper T cells inflammation.

© 2015 John Wiley & Sons Ltd.


Characteristics of CD4 + CD28…

Characteristics of CD4 + CD28 null T cells in atherosclerosis. In patients that…


Regulatory T cells (Tregs) are a suppressive subset of CD4 + T helper (Th) cells important for the regulation of immune responses. The best-characterized Tregs are defined by expression of the transcription factor forkhead box protein 3 (FOXP3) and demethylation of the Treg-specific demethylated region (TSDR) in the FOXP3 locus. Demethylation of this element is thought to be crucial to maintain the stable, high expression of FOXP3 necessary for lineage stability and suppressive function (1, 2). Additional Treg markers include constitutive expression of the high-affinity IL-2Rα chain (CD25) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) (3), along with low expression of the IL-7Rα chain (CD127) (4, 5). CD4 + CD25 + FOXP3 + Tregs can be divided into two main types: thymically derived Tregs (tTregs) and peripherally derived Tregs (pTregs) (6). Although it is difficult to distinguish between tTregs and pTregs phenotypically, both are thought to have an essential role in immune regulation (7).

Because of their immunoregulatory function, Tregs are an attractive therapeutic target in many different immune-mediated diseases, including transplantation, autoimmunity, and autoinflammation (8). An emerging concept is that Tregs are functionally specialized to their local environments (9), with the local milieu of cytokines, metabolites, and catabolites having major effects on the phenotype and function of these cells. In this review, we discuss current knowledge on how environmental factors affect Treg development, maintenance, and function, focusing on key recent findings in the area of cytokines, metabolites, and the microbiome.

How does a person's T cell count indicate AIDS?

HIV destroys CD4 T lymphocytes (helper T cells). Because of this, healthcare professionals measure CD4 levels to monitor HIV progression and AIDS.

Helper T cells are crucial for immune system function and activate after encountering antigens from disease-causing microorganisms. Antigens are biological markers that identify microorganisms such as bacteria and viruses.

When a CD4 count falls below a certain level, a person receives an AIDS diagnosis. The treatment a healthcare professional suggests depends on how low the CD4 count is.

Keep reading to learn more about T cells and their function and the link between T cell level and HIV and AIDS.

T cells grow from stem cells in the bone marrow. They are a type of white blood cell. There are two main types of T cells: helper T cells and killer T cells. Ultimately, it is the killer T cells that attack and kill cells that pathogens have infected.

Helper T cells

Macrophages are another type of white blood cell. They consume disease-causing microorganisms, or pathogens, then present fragments of their antigens to helper T cells. When a helper T cell binds to the antigen fragment that it recognizes, it activates and alerts other white blood cells to the pathogen.

Helper T cells have CD4 proteins on their cell surface, which help them bind to antigen fragments. Because HIV destroys helper T cells, healthcare professionals use a CD4 count to measure CD4 levels and HIV progression.

Killer T cells

After receiving the alert, killer T cells seek out and destroy the pathogen (virus, bacteria, or disease-causing microorganisms). Other white blood cells, such as B lymphocytes, will also activate and produce antibodies in order to protect against the threat.

HIV enters its genetic information into helper T cells to make copies of itself. When this happens, the helper T cells die. This severely disrupts the immune response. Low levels of helper T cells mean killer T cells and other white blood cells do not receive as much information about pathogens in the body. As a result, disease-causing bacteria and viruses multiply with minimal detection.

When the amount of helper T cells falls below 200 cells/mm 3 (cells per cubic millimeter), a person may receive an AIDS diagnosis. But healthcare professionals will also take into account other variables such as overall white blood cell count and the percentage of lymphocytes.

AIDS is the most severe stage of HIV. When a person receives an AIDS diagnosis, their immune system is severely compromised, and they are at risk for opportunistic illnesses. The survival rate without treatment at this stage is typically 3 years .

CD4 T cells are helper T cells. They express, or manifest, a CD4 protein on their cell surface that helps them bind to antigen fragments. These antigen fragments belong to viruses, bacteria, and other microorganisms that could threaten a person’s health. Killer T cells express a CD8 protein on their cell surface.

When activated, helper T cells mobilize other white blood cells to initiate a full immune response. Killer T cells, for example, then seek out the pathogen and destroy it by releasing granzymes, which trigger cell death.

If someone’s helper T cells are below 200 cells/mm 3 , they will likely receive an AIDS diagnosis.

When a person has HIV, a healthcare professional will collect a blood sample and request a CD4 count. The CD4 count helps determine how many helper T cells a person has.

But when analyzing a CD4 count, healthcare professionals must take into account that:

  • CD4 levels could be lower in the morning and fatigue may affect CD4 levels
  • corticosteroid levels could increase or decrease CD4 levels

All people whose helper T cells are below 200 cells/mm 3 should receive a CD4 count every 3–6 months. If treatment is working, a person may only need a CD4 checkup every 6–12 months.

The CD4 count helps healthcare professionals monitor HIV progression and if the person is at risk for opportunistic illnesses.

When a healthcare professional wants a CD4 count, they take a blood sample from a person’s arm.

Side effects of drawing blood may include:

A healthcare professional will likely only need to draw a small amount of blood, so a person should not feel any significant side effects.

Usually, when someone receives an HIV diagnosis, they will start antiretroviral therapy (ART) as soon as possible .

If a person responds well to ART, their CD4 levels may increase by 100–150cells/mm 3 after 1 year.

After analyzing a CD4 count, a healthcare professional can determine if the current care plan is working or if they need to introduce additional treatments.

As soon as CD4 levels drop below 200 cells/mm 3 , a healthcare professional may need to increase ART and administer other drugs to help bolster the immune system against opportunistic illnesses.

All people with HIV should receive a CD4 count every 3–6 months if their CD4 levels are below 200 cells/mm 3 , as this indicates a progression to AIDS. If the treatment is working and the CD4 count is stable, a person may only need a checkup every 6–12 months.

If a person receives an HIV diagnosis in time and starts ART promptly , it is unlikely their condition will progress to AIDS.

Taking ART not only keeps the volume of helper T cells high but also decreases the viral load (the amount of virus in the body).

If someone’s viral load decreases, it may reach an undetectable level. This means if a person keeps up the treatment for their condition, the virus cannot transmit to anyone through sex. Having an undetectable viral load also reduces HIV transmission during birth.

A healthcare professional requests a CD4 count to monitor helper T cell levels. When a person’s CD4 levels drop below 200 cells/mm 3 , the healthcare professional may diagnose that person with AIDS. If someone begins ART promptly after receiving an HIV diagnosis, their condition may never progress to AIDS.

T cells include two main types: helper T cells and killer T cells. Helper T cells express a CD4 protein on their cell surface that helps them bind to antigen fragments. These antigen fragments belong to disease-causing viruses and bacteria. After binding, the helper T cells signal other white blood cells to destroy the pathogen. Killer T cells are another type of T cell that break down pathogens by releasing granzymes that trigger cell death.


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How AIDS Works

Like all viruses, HIV treads the fine line that separates living things from nonliving things. Viruses lack the chemical machinery that human cells use to support life. So, HIV requires a host cell to stay alive and replicate. To reproduce, the virus creates new virus particles inside a host cell, and those particles carry the virus to new cells. Fortunately the virus particles are fragile.

Viruses, including HIV, don't have cell walls or a nucleus. Basically, viruses are made up of genetic instructions wrapped inside a protective shell. An HIV particle, called a virion, is spherical and has a diameter of about one 10,000th of a millimeter.

HIV infects one particular type of immune system cell. This cell is called the CD4+T cell, a type of white blood cell also known as a T-helper cell. In fact, the virus only targets a subset of the T-helper cells: those that have already been exposed to infection. This is because, unlike "naive" cells, the experienced "memory" cells are in constant motion, and HIV uses that motion in a complex way to get inside them. Once infected, the T-helper cell turns into an HIV-replicating cell. T-helper cells play a vital role in the body's immune response. There are typically 1 million T-cells per 1 milliliter of blood. HIV will slowly reduce the number of T-cells until the person develops AIDS.

HIV is a retrovirus, which means it has genes composed of ribonucleic acid (RNA) molecules. Like all viruses, HIV replicates inside host cells. It's considered a retrovirus because it uses an enzyme, reverse transcriptase, to convert RNA into DNA [source: Lu et al.].

To understand how HIV infects the body, let's look at the virus's basic structure:

Th17 cell activation and differentiation

Like other subsets of T helper cells, Th17 cells differentiate from naive CD4 + cells in the periphery in response to T cell receptor (TCR) antigen stimulation and activating cytokines secreted by antigen-presenting cells [6]. While differentiation was originally believed to be induced by IL-23, it was later demonstrated that Th17 development occurred independently of this cytokine. However, IL-23 is still thought to be important for Th17 maintenance and proliferation, and its receptor (IL-23R) is upregulated in activated Th17 cells [6]. The critical cytokine mediators of Th17 differentiation have instead been identified to be TGFβ in combination with IL-6 or IL-21 [6,7]. IL-6 and IL-21 drive expression of Th17 transcriptional regulators via STAT3 signaling, committing CD4 + T cells to the Th17 lineage. Defects in this signaling pathway have been associated with decreased expression of IL-23R, key Th17-associated transcription factors, and effector cytokines such as IL-17A and IL-17F [7].

A candidate master regulator of Th17 differentiation was first identified as RORγt, a member of the retinoic acid–related orphan nuclear hormone receptor family [6]. This transcription factor was found to induce expression of IL-17A and IL-17F, and its deficiency was associated with reduced, but not completely absent, Th17 development and function [6,7]. Later studies identified RORα, a related transcription factor, could also drive Th17 differentiation and cytokine expression in response to STAT3 in a similar manner as RORγt [8]. RORα and RORγt act synergistically to promote Th17 commitment, and combined deficiencies in both factors results in complete inhibition of Th17 development [8].

Other transcription factors that play a role in Th17 development are IRF4, BATF, and AHR. IRF4 is thought to be upstream of RORγt, as the ability of naive CD4 + T cells to upregulate RORγt expression is reduced in its absence, but its exact role in Th17 biology is not fully understood [9]. AHR is a nuclear factor shared with T regulatory cells but expressed at higher levels in Th17 cells, and while its deficiency does not impact Th17 differentiation, the production of effector cytokines, particularly IL-22, is significantly diminished [10]. Lastly, BATF has been demonstrated to be necessary for generation of Th17 cells and expression of their associated cytokines, despite the observation that BATF is not unique to the Th17 lineage and that BATF-deficient cells are still capable of inducing RORα and RORγt [11].

The Th17 lineage exhibits a high degree of plasticity and has been observed to trans-differentiate into other CD4 + T helper subtypes in response to changing environmental cues. T regulatory cells are another T helper subset that depends on TGFβ for its differentiation increasing concentrations of this cytokine tend to skew naive cells towards Foxp3 expression, which is strongly inhibitory to Th17 development and instead drives commitment towards a regulatory phenotype [12]. Despite this, high levels of IL-6 and resultant STAT3 signaling can downregulate Foxp3 expression in favor of Th17-related genes in TGFβ-induced T regulatory cells, particularly in the presence of IL-1 [13]. While trans-differentiation of Th17 cells has been mainly observed with the Th1 and T regulatory subsets, evidence also exists of shared functions with Th2, T follicular helper, and TR1 cells [14]. The observation that multiple transcriptional master regulators of different CD4 + T helper cell subsets can be co-expressed further confirms the potential for functional flexibility between these lineages [15].

Figure 1. Overview of Th17 differentiation. Naive CD4 + T cells begin their polarization towards the Th17 lineage following STAT3 signaling and RORγt upregulation induced by IL-6 or IL-1 in the presence of TGFβ. IL-21 production maintains Th17 commitment in an autocrine manner, and IL-23 from antigen presenting cells promotes maturation, survival, and effector functions.

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T follicular helper (TFH) cells play a crucial part in the development of humoral immunity by controlling the formation of, and the cellular reactions that occur in, germinal centres. Within these organized lymphoid tissue microstructures, B cells proliferate and somatically mutate to produce long-lived, high-affinity plasma cells and memory B cells. TFH cells exhibit unique molecular, cellular and tissue-dynamic features that are integral to their development and function but that are not necessarily compatible with the classical paradigm of effector CD4 + T cell differentiation. Here, I discuss recent advances in TFH cell biology and their implications for our understanding of T cell differentiation and memory in humoral immunity from spatiotemporal and functional perspectives.


The immune system is comprised of a variety of cell types that work in a highly organized fashion to protect the body from infection and minimize tumor formation. This organizational process is largely carried out by the adaptive immune system with CD4 + T helper (Th) cells acting to trigger inflammation during infection and also suppress unwanted immune responses to non-harmful stimuli (i.e. allergens, food or normal body microflora). The dual nature (i.e. activator and suppressor) of Th cells is possible due to their unique ability to sense the environment and change their function based on these environmental cues.

Autoimmune disease occurs when the balance between the inflammatory and regulatory functions of Th cells is disrupted, resulting in excess inflammation that alters physiological processes. Inflammatory bowel disease (IBD) and graft-versus-host disease (GVHD) are two forms of intestinal autoimmune disease and are characterized by the accumulation of highly reactive inflammatory T cells in the intestines. However, the exact mechanisms by which inflammatory Th cells arise during inflammation and cause disease are unclear.

In the Olson lab, our goal is to better understand how CD4 + T helper cells drive intestinal inflammation by addressing these key questions:

1) What signals drive the generation of pathogenic/inflammatory Th cells in the intestines?

2) How do pathogenic/inflammatory T helper cells contribute to disease?

3) Can we therapeutically target factors that drive the generation of pathogenic T helper cells or their functional byproducts to eliminate or reduce disease?

My laboratory uses a combination of cell and molecular biology approaches to examine signaling pathways associated with T helper cell differentiation. We also utilize pre-clinical models of disease, and high throughput culturing and RNA/protein profiling techniques to identify disease mechanisms and novel mediators of inflammation.

Watch the video: Helper T Cells (February 2023).