T Cell Development ? ? ? ?? ? ?. Role of the thymus in T cell development Required for T cell...

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Transcript of T Cell Development ? ? ? ?? ? ?. Role of the thymus in T cell development Required for T cell...

Page 1: T Cell Development ? ? ? ?? ? ?. Role of the thymus in T cell development Required for T cell development –Neonatal thymectomy –Nude mice Shapes T cell.

T Cell Development

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Page 2: T Cell Development ? ? ? ?? ? ?. Role of the thymus in T cell development Required for T cell development –Neonatal thymectomy –Nude mice Shapes T cell.
Page 3: T Cell Development ? ? ? ?? ? ?. Role of the thymus in T cell development Required for T cell development –Neonatal thymectomy –Nude mice Shapes T cell.

Role of the thymus in T cell development

• Required for T cell development– Neonatal thymectomy– Nude mice

• Shapes T cell repertoire– Transplant experiments

Page 4: T Cell Development ? ? ? ?? ? ?. Role of the thymus in T cell development Required for T cell development –Neonatal thymectomy –Nude mice Shapes T cell.

Shaping the T cell repertoire

Page 5: T Cell Development ? ? ? ?? ? ?. Role of the thymus in T cell development Required for T cell development –Neonatal thymectomy –Nude mice Shapes T cell.

What are thymocytes doing?

• MigratingMigrating

• Contacting stromal cells

• Changing phenotype

• Expressing TCRs

• Undergoing selection

Page 6: T Cell Development ? ? ? ?? ? ?. Role of the thymus in T cell development Required for T cell development –Neonatal thymectomy –Nude mice Shapes T cell.
Page 7: T Cell Development ? ? ? ?? ? ?. Role of the thymus in T cell development Required for T cell development –Neonatal thymectomy –Nude mice Shapes T cell.

What are thymocytes doing?

• Migrating

• Contacting stromal cellsContacting stromal cells

• Changing phenotype

• Expressing TCRs

• Undergoing selection

Page 8: T Cell Development ? ? ? ?? ? ?. Role of the thymus in T cell development Required for T cell development –Neonatal thymectomy –Nude mice Shapes T cell.

Thymocyte:stromal cell interactions

Page 9: T Cell Development ? ? ? ?? ? ?. Role of the thymus in T cell development Required for T cell development –Neonatal thymectomy –Nude mice Shapes T cell.

What are thymocytes doing?

• Migrating

• Contacting stromal cells

• Changing phenotypeChanging phenotype

• Expressing TCRs

• Undergoing selection

Page 10: T Cell Development ? ? ? ?? ? ?. Role of the thymus in T cell development Required for T cell development –Neonatal thymectomy –Nude mice Shapes T cell.

T Cell Development in the Thymus

Page 11: T Cell Development ? ? ? ?? ? ?. Role of the thymus in T cell development Required for T cell development –Neonatal thymectomy –Nude mice Shapes T cell.

What are thymocytes doing?

• Migrating

• Contacting stromal cells

• Changing phenotype

• Expressing TCRsExpressing TCRs

• Undergoing selection

Page 12: T Cell Development ? ? ? ?? ? ?. Role of the thymus in T cell development Required for T cell development –Neonatal thymectomy –Nude mice Shapes T cell.

T Cell Development in the Thymus

Page 13: T Cell Development ? ? ? ?? ? ?. Role of the thymus in T cell development Required for T cell development –Neonatal thymectomy –Nude mice Shapes T cell.
Page 14: T Cell Development ? ? ? ?? ? ?. Role of the thymus in T cell development Required for T cell development –Neonatal thymectomy –Nude mice Shapes T cell.
Page 15: T Cell Development ? ? ? ?? ? ?. Role of the thymus in T cell development Required for T cell development –Neonatal thymectomy –Nude mice Shapes T cell.

What are thymocytes doing?

• Migrating

• Contacting stromal cells

• Changing phenotype

• Expressing TCRs

• Undergoing selectionUndergoing selection

Page 16: T Cell Development ? ? ? ?? ? ?. Role of the thymus in T cell development Required for T cell development –Neonatal thymectomy –Nude mice Shapes T cell.

T and B cell receptors

Page 17: T Cell Development ? ? ? ?? ? ?. Role of the thymus in T cell development Required for T cell development –Neonatal thymectomy –Nude mice Shapes T cell.

• Based on specificity of TCR• Produces “central tolerance” to self antigens• Produces T cell repertoire biased toward self

MHC + peptide specificities• Consists of 3 levels of selection

– Positive Selection– Negative Selection– Death by neglect

Thymic Selection

Page 18: T Cell Development ? ? ? ?? ? ?. Role of the thymus in T cell development Required for T cell development –Neonatal thymectomy –Nude mice Shapes T cell.

Positive selection

Page 19: T Cell Development ? ? ? ?? ? ?. Role of the thymus in T cell development Required for T cell development –Neonatal thymectomy –Nude mice Shapes T cell.

Positive selection

Page 20: T Cell Development ? ? ? ?? ? ?. Role of the thymus in T cell development Required for T cell development –Neonatal thymectomy –Nude mice Shapes T cell.

Positive selection

Page 21: T Cell Development ? ? ? ?? ? ?. Role of the thymus in T cell development Required for T cell development –Neonatal thymectomy –Nude mice Shapes T cell.

Negative selection

Page 22: T Cell Development ? ? ? ?? ? ?. Role of the thymus in T cell development Required for T cell development –Neonatal thymectomy –Nude mice Shapes T cell.

Thymic Selection

Page 23: T Cell Development ? ? ? ?? ? ?. Role of the thymus in T cell development Required for T cell development –Neonatal thymectomy –Nude mice Shapes T cell.
Page 24: T Cell Development ? ? ? ?? ? ?. Role of the thymus in T cell development Required for T cell development –Neonatal thymectomy –Nude mice Shapes T cell.

CD4/CD8 lineage commitment

Page 25: T Cell Development ? ? ? ?? ? ?. Role of the thymus in T cell development Required for T cell development –Neonatal thymectomy –Nude mice Shapes T cell.

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