Immunology

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Immunology

• Chapter 9
• T-cell Development

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• Progenitor T cells migrate from bone marrow to
  thymus
• T cells can be grown in vitro in absence of
  thymic fragments
• Grown on bone marrow stem cells with Notch
  protein
• Notch protein is key in determining T-lineage
  specification

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• Progenitor T cells migrate to thymus
• At about 8th or 9th week of gestation in humans
• T cell maturation involves rearrangements of the
  germ-line TCR genes
• In thymus, thymocytes proliferate and
  differentiate

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• Selection process in thymus
• Positive selection
• Survival of only T cells whose TCRs recognize
  self-MHC molecules
• Negative selection
• Eliminates T cells that react too strongly with
  self MHC or MHC with self-peptides

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T-cell Development

• Begins with arrival of small numbers of lymphoid
  precursors migrating from blood to thymus
• When they do arrive in thymus, T-cell precursors
  dont express signature surface markers (CD3,
  CD4, and CD8)
• Do not express RAG-1 or RAG-2 that are necessary
  for gene rearrangement

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T-cell Development

• During 3 week development, differentiating T
  cells pass through stages of development based on
  surface phenotypes

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DN Double negative CD4- and CD8- DP
Double positive CD4 and CD8
C-kit receptor for stem cell growth factor CD44
an adhesion molecule CD25 - alpha chain of
IL-2 receptor
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• T cell development is expensive for host
• 98 of all thymocytes do not mature, die by
  apoptosis within thymus

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Insertion of rearranged TCR genes suppress other
gene rearrangements in these mice
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Exit from Thymus and final maturation

• Mature T cells that survive the selection process
  leave the thymus
• Recent thymic emigrants

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Treg Cells

• Shown to inhibit proliferation of other T cells
  in vitro
• CD4CD25
• Shown to inhibit development of autoimmune
  diseases

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Cell Death and T Cell Populations

• Apoptosis plays critical role
• Deletion of potentially autoreactive thymocytes
• Deletion of T cell populations after activation
• Fas and FasL pathway to induce self death