• Naive B and T cells need IL-7 to survive
• IL-7 made by stromal (non-bone marrow derived cells) ie fibroblasts
• T cells also need "tickling" of TCR through MHC I or MHC II for survival (no antigen specific)
• Estimated that lifespan of naive lymphocyte = 3 months

• Naive T cells become activated, differentiate into effector cells, then some become memory cells
• Important to remember that all T cells act on host cells, not directly on pathogens
• The host cells that T cells exert their effector functions on are target cells

• Activation: activation in secondary lymphoid organs
• Naive, non specific
• Expansion: clonal expansion, effector molecules
• Contraction: effector molecules
• Memory: specific, remember antigen

• Changes both in cell surface molecules after activation, as well as the induction of effector molecules
• Some of these properties also change when T cells become memory cells

• L-selectin: Resting (+), Activated (-)
• LFA-1: Resting (+), Activated (++), memory (high)
• CD44: Resting (+), Activated (++), memory (high)
• CCR7: high (naive), low (activated), memory (high/low)

• CD44: Naive (+), Effector (+++), Memory (+++), cell-adhesion
• CD62L:Naive (+++), Effector (-), Memory (some +++), receptor for homing to lymph node
• CCR7:Naive (+++), Effector (+/-), Memory (some +++),  chemokine receptor for homing to lymph node
• Bcl-2:Naive (++), Effector (+/-), Memory (+++), cell survival
• Interferon-gamma:Naive (-), Effector (+++), Memory (+++), effector cytokine;mRNA present and protein made - activation
• Granzyme B:Naive (-), Effector (+++), Memory (+/-), effector cell killing
• FasL:Naive (-), Effector (+++), Memory (+), effector cell killing
• CD122:Naive (+/-), Effector (++), Memory (++), part of receptor for IL-15, and IL-2
• CD25: Naive (-), Effector (++), Memory (-), part of receptor IL-2
• CD127: Naive (++), Effector (-), Memory (+++), part of receptor IL-7

• alpha4beta7: helps get activated T cells into intestine
• alpha4beta1 (VLA4): more generalized migration troughout body
• Use of antibody blocking alpha4 integrin (Tysabri) has been used to treat MS - has been associated with fatal neuro-demylination (PML) in a small proportion of patients

• Naive T cells bind to DC to sample MHC for presence of specific cognate peptide. Done with adhesion molecules, like LFA-1. Most dont result in recognition
• When cognate present, and signal received through TCR, a conf. change in LFA-1 on T cells, increases affntiy for ICAM-1 and ICAM-2 on DC. Results in stronger int. between DC and T cell

• 3 signals must be delivered to T cell from APC
• Signal 1 = MHC/peptide + TCR (activation)
• Signal 2 = co-stim B7.1 or B7.2 on DC engages CD28 on T cell (survival)
• Signal 3 = cytokine secreted by APC (differentiation)
• IL-2 is critical cytokine made by T cells after signal 1 + signal 2

• guided to sites of infection, by inflammation, chemokines, and adhesion molecules
• Activated T cells: can enter any tissue (inflammed or not)
• Inflammation does help recruit more cells however (chemokines)

1. Stimulation/Recognition
• Naive T cell, MHC binds TCR, B7 binds CD28
2. Proliferation/Differentiation
• IL-2 production
3. Active/Effector Function
• kills virus infected target cells

• Initial int. w/ target cell LFA-1, ICAM-1 nonspecific adhesion molecules
• No antigen-specific int. = cell seperation
• Antigen specific recognition = stable pairing, tight binding, and release of effector molecules
• Once effectors have killed/lysed target CD8 moves onto next infected target w/ specific antigen binding motif

• APC stimulates effector CD4 T cell to induce CD40L and IL-2
• Stimulation of APC through CD40 increases B7 and 4-IBBL, which co-stimulates naive CD8 T cell

• Effector CD4 can help CD8 during priming
• Occurs through CD40L (ligand) on CD4 interacting with CD40 on APC
• Interaction yields IL-2 production from CD4 which acts as a survival and proliferation signal for CD8
• CD40 ligation of APC by CD4 CD40L causes APC to increase co-stim, like B7 for use by CD8
• IL-2 only made by activated T cells

Different subsets of effector T cells can modulate the effector funtions of others

• Activated Th2
• Secrete TGF-B and IL-10
• Inhibits activation/growth of Th1 cells
• Treg
• supress activation/proliferation naive T cells (TGF-B)
• Activated Th1
• Secret IFN-gamma
• acts on Th2 cells inhibiting proliferation

• Need IL-15 to survive
• Do not need antigen recognition or MHC I or II interactions for longevity
• Can persist for 20+ years

• Greater than primary response
• Due to previous infection and already low present amount of memory T cells