Transcript Kuby Immunology 6/e

Chapter 9
T-cell Development
Dr. Capers
Kindt • Goldsby • Osborne
Kuby IMMUNOLOGY
Sixth Edition
Chapter 10
T-Cell Maturation, Activation,
and Differentiation
Copyright © 2007 by W. H. Freeman and Company


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 Tlineage specification

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


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
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
T-cell Development

During 3 week development,
differentiating T cells pass through
stages of development based on surface
phenotypes
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

T cell development is expensive for host
○ 98% of all thymocytes do not mature, die by
apoptosis within thymus
Insertion of rearranged TCR genes suppress
other gene
rearrangements in these mice
Exit from Thymus and final maturation

Mature T cells that survive the selection
process leave the thymus
○ Recent thymic emigrants
Treg Cells
Shown to inhibit proliferation of other T
cells in vitro
 CD4+CD25+
 Shown to inhibit development of
autoimmune diseases

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