T cells are lymphocytes, a type of peripheral blood mononuclear cells (PBMC, also known as white blood cells). There are two types of T cells: memory T cells and effector T cells. These cells are known to be critical factors in the body's immune responses to pathogens.
T cells are a component of the cell-mediated immune response. Cell-mediated immunity is an immune response that protects the body against different pathogens (e.g., Mycobacterium tuberculosis). There has been a growing realization of the importance of T cells in diagnosing disease.
Memory T Cells
Memory T cells carry the body's long-term immunity or 'memory' of an infection-causing pathogen and are present after any infection. Memory T cells are generally not able to fight the infection directly, but they enable the body to react quickly and control a recognized pathogen if encountered later. When memory T cells recognize a pathogen they produce messenger molecules, known as cytokines. These cytokines attract other memory T cells to the area that initiate proliferation of the memory cells through cell division, producing effector T cells.
Effector T Cells
Effector T cells fight the pathogen (e.g., M. tuberculosis) directly and come in various forms, designed to kill different pathogens in different ways. Most are short-lived and die off when the pathogen is cleared from the body. Due to the short life of effector T cells, their continuing presence indicates the cellular immune response is currently encountering and fighting a pathogen somewhere in the body. Measuring the presence of effector T cells in a sample therefore diagnoses an ongoing infection. (In contrast, the presence of memory T cells, for example, would indicate that someone had been infected with the pathogen at some point in the past).
Interferon Gamma
T cells release interferon gamma (IFN-γ) along with a number of other cytokines to fight the infecting organism. Specific epitopes on the infecting organism have to be recognized by the T cells to initiate the release of IFN-γ. The T-SPOT®.TB test uses very specific antigens, ESAT-6 and CFP 10, to stimulate effector T cells.
ESAT-6 and CFP 10 Antigens
One of the major drawbacks of the Tuberculin Skin Test is the cross-reaction it has with the BCG vaccine. The purified protein derivative that it is injected in the skin test is a crude mixture of around 200 peptides extracted from dead MTB cells. Many of these proteins have common epitopes to BCG, and environmental mycobacteria, so the skin test will cross react with these.
An analysis of the MTB genome identified an area that was lost from M. bovis when it was being passaged by Calmette and Guerin to produce the BCG vaccine. This lost area is known as the Region of Difference 1, or RD1. Nine proteins are made by this genomic area including ESAT-6 and CFP 10.
Therefore, if the T cells of a person with an M. tuberculosis infection encounter these proteins they will recognize them as being foreign and will respond by releasing interferon gamma.
Since these RD1 proteins are not found in BCG or most environmental mycobacteria, T cells from a person who has been BCG vaccinated or who is infected with environmental mycobacteria will not respond to the ESAT-6 and CFP 10 antigens as their T cells will not recognize them unless they have subsequently become infected with M. tuberculosis.
The T-SPOT.TB test utilizes both ESAT-6 and CFP 10. Test results are therefore not affected by BCG vaccination and most common non-tuberculosis mycobacteria.
T-SPOT® technology is an innovative method to detect and quantify effector T cells.
