Regulatory T Cells
For many years, different laboratories — usually using different protocols — have found evidence of lymphocytes that suppress immune responses: antibody-mediated and/or cell-mediated. But these cells have been difficult to study, primarily because of the difficulty is isolating clones; that is, populations descended from a single cell.
Originally called suppressor T cells (Ts cells), the most promising recent candidates have been given other names. We shall look at three examples:
Most CD4+ T cells belong to either the Th1 or Th2 subsets. [Link to discussion]
However some 5–10% of them do not. These so-called T-regulatory (Tr) cells
- express a transmembrane protein (called CD25) that is alpha chain of the receptor for interleukin-2 (IL-2).
- Like other T cells, they also express the αβ
(alpha-beta) T-cell receptor for antigen (TCR) and can only be activated if
- it binds to the peptide-class II MHC molecule for which it is specific. [Link to discussion] and
- the cell also receives costimulation from B7 molecules (CD80 and CD86) on the antigen-presenting cell. [More]
- However, if activated, they begin to secrete large amounts of interleukin 10 (IL-10) and often some transforming growth factor-beta (TGF-β) as well.
- Both these lymphokines are powerful immunosuppressants inhibiting
- The antigenic peptides recognized by their TCRs tend to be self-peptides and perhaps the major function of Tr cells is to inhibit other T cells from mounting an immune attack against self components; that is, to protect the body against autoimmunity.
- This idea receives support, in mice at least, from these observations:
- Destruction of their Tr cell population causes mice to spontaneously develop a spectrum of autoimmune diseases.
- Nude mice (which have no T cells of their own — link to discussion) develop autoimmune disease if they are given CD4+ T cells that have been depleted of the CD25+ population; that is, lack Tr cells.
- Tr1 cells resemble Tr cells in several ways, although they do not express large amounts of CD25 on their surface.
- They require IL-10 for their formation and, once mature, secrete large amounts of it. (Perhaps Tr1 cells are simply normal CD4+ T cells that become permanently altered by exposure to IL-10.)
- Tr1 cells are abundant in the intestine, and their chief function may be to make the animal tolerant to the many antigens that are part of its diet.
- This idea is supported by the observation that mice that cannot make enough IL-10 develop inflammation of the large intestine, and giving IL-10 to them cures it.
- Th3 cells are also prevalent in the intestine, but unlike Tr1 cells, their main lymphokine is TGF-β.
- Also like Tr1 cells, they suppress immune responses to ingested antigens. It has long been known that eating antigenic material can induce a condition of "oral tolerance". Th3 and/or Tr1 cells may be the responsible agents.
Further research will be needed to sort out the relationships between these (and other) T cells that suppress immune responses. This work will be important because it could lead to improvements in
8 November 2004