1. Chapter 9 T-cell Development
Immunology

2. 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

3. 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

4. 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

5. 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 don’t express signature surface markers (CD3, CD4, and CD8)
Do not express RAG-1 or RAG-2 that are necessary for gene rearrangement

6. T-cell Development
During 3 week development, differentiating T cells pass through stages of development based on surface phenotypes

7. 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

8. T cell development is expensive for host
98% of all thymocytes do not mature, die by apoptosis within thymus

11. Insertion of rearranged TCR genes suppress
other gene
rearrangements in these mice

12. Exit from Thymus and final maturation
Mature T cells that survive the selection process leave the thymus
Recent thymic emigrants

13. Treg Cells Shown to inhibit proliferation of other T cells in vitro
CD4+CD25+
Shown to inhibit development of autoimmune diseases

14. 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