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T Cells: Soldiers and Spies--The Surveillance and Control of Effector T Cells by
Regulatory T Cells
#MMPMID25876770
Hall BM
Clin J Am Soc Nephrol
2015[Nov]; 10
(11
): 2050-64
PMID25876770
show ga
Traditionally, T cells were CD4+ helper or CD8+ cytotoxic T cells, and with
antibodies, they were the soldiers of immunity. Now, many functionally distinct
subsets of activated CD4+ and CD8+ T cells have been described, each with
distinct cytokine and transcription factor expression. For CD4+ T cells, these
include Th1 cells expressing the transcription factor T-bet and cytokines IL-2,
IFN-?, and TNF-?; Th2 cells expressing GATA-3 and the cytokines IL-4, IL-5, and
IL-13; and Th17 cells expressing ROR?t and cytokines IL-17A, IL-17F, IL-21, and
IL-22. The cytokines produced determine the immune inflammation that they
mediate. T cells of the effector lineage can be naïve T cells, recently activated
T cells, or memory T cells that can be distinguished by cell surface markers. T
regulatory cells or spies were characterized as CD8+ T cells expressing I-J in
the 1970s. In the 1980s, suppressor cells fell into disrepute when the gene for
I-J was not present in the mouse MHC I region. At that time, a CD4+ T cell
expressing CD25, the IL-2 receptor-?, was identified to transfer transplant
tolerance. This was the same phenotype of activated CD4+ CD25+ T cells that
mediated rejection. Thus, the cells that could induce tolerance and undermine
rejection had similar badges and uniforms as the cells effecting rejection.
Later, FOXP3, a transcription factor that confers suppressor function, was
described and distinguishes T regulatory cells from effector T cells. Many
subtypes of T regulatory cells can be characterized by different expressions of
cytokines and receptors for cytokines or chemokines. In intense immune
inflammation, T regulatory cells express cytokines characteristic of effector
cells; for example, Th1-like T regulatory cells express T-bet, and IFN-?-like Th1
cells and effector T cells can change sides by converting to T regulatory cells.
Effector T cells and T regulatory cells use similar molecules to be activated and
mediate their function, and thus, it can be very difficult to distinguish
soldiers from spies.
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