The human immune system protects the body from invading pathogens like viruses and bacteria, as well as abnormal cells. T cells, a type of lymphocyte, play a central part in this defense by recognizing and neutralizing threats. Within the diverse population of T cells, certain subsets develop specialized functions. One such specialized subset is the Terminally Differentiated Effector Memory T cell Re-expressing CD45RA (TEMRA) cell.
Understanding TEMRA Cells
TEMRA cells are a distinct T cell sub-population representing a late stage of development. They are considered terminally differentiated, meaning they have reached an advanced specialization with limited ability to multiply further. These cells develop from effector memory T cells, which are already experienced in fighting specific threats.
A defining feature of TEMRA cells is their re-expression of the CD45RA molecule, a marker typically found on “naïve” T cells that have not yet encountered an antigen. This re-expression can sometimes lead to their misidentification. Unlike naïve cells, TEMRA cells lack CD27 and CD28 co-stimulatory markers, often present on less differentiated T cells. Internally, TEMRA cells are characterized by high levels of cytotoxic molecules like perforin and granzyme B, equipping them for potent cell-killing.
How TEMRA Cells Operate
TEMRA cells are distinguished by their immediate and potent effector capabilities, particularly cytotoxic activity. They are “pre-armed” to eliminate infected or abnormal cells upon re-encountering a familiar threat. This rapid response is achieved through swift release of pre-formed cytotoxic proteins stored in their granules.
When a TEMRA cell recognizes its target, it forms a close contact, known as an immunological synapse, and directs the release of these molecules. Perforin creates pores in the target cell’s membrane, allowing other molecules to enter. Granzymes, which are proteases, enter through these pores and activate enzyme cascades within the target cell, leading to programmed cell death (apoptosis). This direct cell-killing mechanism allows TEMRA cells to effectively clear infected or cancerous cells and contribute to immune surveillance.
TEMRA Cells in Immune Responses and Aging
TEMRA cells play a significant role in long-term immunity, particularly in chronic viral infections. Their numbers often increase during persistent infections like Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV). This accumulation of TEMRA cells is a result of continuous stimulation by these lingering viruses, contributing to sustained immune surveillance against them.
In older individuals, TEMRA cells accumulate and are often associated with immunosenescence, the age-related decline of the immune system. While their increased presence can be beneficial for maintaining protection against previously encountered pathogens, particularly CMV, they can also contribute to chronic inflammation.
This chronic inflammation, sometimes called “inflammaging,” can potentially reduce the immune system’s ability to respond effectively to new challenges, such as vaccine responses, and has been linked to age-related diseases like cardiovascular disease and neurodegenerative disorders.
Differentiating TEMRA Cells from Other T Cells
TEMRA cells stand apart from other T cell subsets due to their unique combination of characteristics. Naïve T cells, for instance, have not yet encountered an antigen and are typically marked by CD45RA and CD62L, allowing circulation through lymphoid organs.
Central memory T cells (TCM) express CD62L and CCR7, enabling them to return to lymph nodes where they can rapidly proliferate upon re-encountering an antigen. Effector memory T cells (TEM), on the other hand, lack CD62L and CCR7, circulating in peripheral tissues and possessing immediate effector functions, though less potent than TEMRA cells.
TEMRA cells, while re-expressing CD45RA like naïve T cells, differ fundamentally in function and differentiation state. They are considered terminally differentiated, possessing high cytotoxic capabilities and reduced proliferative capacity compared to central and effector memory T cells. Their migratory patterns also differ; they are equipped for direct migration to inflamed tissues rather than primarily recirculating through lymphoid organs. This distinction highlights TEMRA cells as a highly specialized end-stage of T cell differentiation, optimized for rapid and potent responses to persistent or recurring threats.