How do T cells respond to lymphopenia

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How do T cells respond to lymphopenia?
Esen Sefik Daniele Santoni Daniel
Hebenstreit Yuki Kimura Supervisors Cameron
Wellard Uri Hershberg Phil Hodgkin
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Key Terms

• Lymphopenia
• means emptying of lymphocytes and can be
  induced genetically in rag-/- mice and by
  irradiation. The induction of a lymphopenic state
  can lead to enhanced immune responses by making
  room for lymphoid organs for T cells to seed and
  develop.
• Lymphopenia-Induced proliferation
• occurs during lymphopenic episodes induced by
  natural infection or chemotherapeutic or
  radiotherapeutic treatment and during
  development of immune system

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X-ray
A. Isolate Splenocytes and purify for CD8 T
cells
B. CD8 T cell depletion by sublethal ?
irradiation ( 800 rad) in naïve mice
C. Transfer CD8 T cells to the host.
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Memory like T cells survive and proliferate
preferentially in irradiated hosts
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Pre-transfer d10
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Rate of proliferation of memory like cells
increase 4X
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Pre-transfer d10
CFSE
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How do T cells respond to lymphopenia?
100
50
CD8 T cells
Time
Memory Like T cells
Naïve T cells
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Thymic input Proliferation Differentiation Death
MEMORY
NAIVE
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Simulation rules (Homeostatic)

• Rules Rate Description
• . -gt N a Naive cells from Thymus
• N -gt M kn,m Differentiation of Naive cell into
  Memory cell
• N -gt 2N kn,p Proliferation of Naive cell
• M -gt 2M km,p Proliferation of Memory cell
• N -gt . kd Death Naive cell
• M -gt . kd Death Memory cell

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Simulation equations (Homeostatis)

• dN/dt a -kn,m N kn,p N -kd (NM)N
• dM/dt kn,m N km,p M -kd (NM)M

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Homeostasis
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Simulation rules (Lymphopenia)

• Rules Rate Description
• . -gt H a Naive Host cells
• N -gt M kn,m Differentiation of Naive into
  Memory
• N -gt 2N kn,p Proliferation of Naive cell
• M -gt 2M km,p Proliferation of Memory cell
• N -gt . kd Death Naïve cell
• M -gt . kd Death Memory cell
• H -gt . kd Death Naïve Host cell

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Simulation equations (Lymphopenia)

• dN/dt -kn,m N kn,p N -kd
  (NMH)N
• dM/dt kn,m N 4km,p M -kd
  (NMH)M
• dH/dt a- kd (NMH)H

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Lymphopenia w/out proliferation of host naïve
cells
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Simulation equations (Lymphopenia)

• dN/dt -kn,m N kn,p N -kd
  (NMH)N
• dM/dt kn,m N 4km,p M -kd
  (NMH)M
• dH/dt a- kd (NMH)H kn,p H

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Lymphopenia w/ proliferation of host naïve cells
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of Naïve to Memory like cells to total T cells
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IL-7 Treatment increases the number of Memory T
cells.
Hand, Morre and Kaech Supp. Fig 3
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