Lecture 11 (6A) - Other T cell subsets Flashcards
Peripheral tolerance
regulatory T cells (T-reg)
regulatory T cells are able to prevent other T cells from generating an immune response to a particular antigen
Regulatory T cells are able to
prevent other T cells from generating an immune response to a particular antigen
Naturally occurring CD4+ T-reg
CD4+
CD25+
Foxp3+
Inducible CD4+ T-reg
Tr1
TH3
and anergic
Other types of cells have regulatory activity
NKT cells
γδ T cells
CD8+ T-reg
Tolerance
to keep the immune system from attacking itself
Central tolerance
make T and B cells, then scan for autoreactive and kill
• detect, response, kill it and it’s gone - final
Peripheral tolerance
few self reactive escape into body - regulatory T cells kill them
• may suppress response through life
Regulatory T cells actively and dominantly
suppress self-reactive T cells that exist in the normal periphery
Autoimmune disease
may develop as a consequence of altered balance between T-reg cells and self-reactive effector T cells
CD25
kills T-reg cells –> autoimmunity
Regulatory T cells were discovered by
Shimon Sakaguchi
• working on white mice
White mouse thymectomized at day 1 or 2
autoimmunity
White mouse thymectomized at day 4 or later
healthy mouse
Autoimmunity can be described as a balance between
regulatory T cells and effector T cells
In the white mouse T-regs are made
after day 4
• at birth lots of DN and DP but few actual CD4 cells
• at birth CD4 start to be produced, some are self-reactive
• this means they need regulatory T cells to ensure they don’t get autoimmunity
• T reg not made until day 4
• remove thymus before day 4 = make some self-reactive but no T-reg
• after day 4 some self-reactive but also some police cells (T-reg)
CD4+ CD25+ cells are
naturally occurring regulatory T cells
Mouse without T cells or B cells
• purified cells from a normal mouse
• gave the SCID mouse only CD4+ CD25- cells (effector)
–> gastritis (autoimmune disease)
-of course there were some autoreactive T cells in the mix but no regulatory T cells to protect them
• gave the SCID mouse CD4+ CD25- (effector) and
CD4+ CD25+ (reguatory) cells
–> no gastritis
CD4+ CD25+
CD4+ CD25-
CD4+ CD25 + == regulatory
CD4+ CD25 - == effector
“Naturally occuring” regulatory T cells
- CD4+ CD25+ T-regs
- have a TCRαβ that is thought to recognize self-antigens
- express a gene called Foxp3 (master gene for T-regs)
- Foxp3 turns on many genes that turn T cells into regulatory T cells (CRLA-4, GITR, CD25)
CD4+ CD25+ T-regs express
Foxp3 - the “master” gene for T-regs
• transcription factor
Foxp3 turns on many genes that
turn T cells into regulatory T cells
• CTLA-4
• GITR
• CD25
IPEX syndrome (stands for)
immune dysregulation, polyendocrinopathy, enterophthy, X-linked
• scurfy mouse naturally without Foxp3