Author: V. Dimov, M.D., Allergist/Immunologist and Assistant Professor at University of Chicago
Reviewer: S. Randhawa, M.D., Allergist/Immunologist and Assistant Professor at LSU (Shreveport) Department of Allergy and Immunology
T-helper cells subsets
There are 2 "balancing systems" - Th1 vs. Th2 and Th17 vs. T regs:
Th1 - infection
Th2 - allergy
Th17 - autoimmunity
T-reg - supression
T-bet - T-bet is a bridge between innate and adaptive immunity (http://buff.ly/1aD6h8s).
Mnemonic: only 1, 2, 4; double, 2 x 2 = 4
Mnemonic: double, 3 x 2 = 6
Mnemonic: 1 + 6 = 7
Mnemonic: "5/3 Bank", TGF/Five
Chemokine receptors and T-helper cells
Mnemonic: 3 x 1 = 3, 5 x 1 = 5
CCR4, CCR8, CXCR4
Mnemonic: 4 x 2 = 8
Four - CXCR4 (CD4) - also involved in WHIM syndrome (PIDD).
A mutation of CXCR4 causes a phagocytic defect called WHIM syndrome (Warts, Hypogammaglobulinemia, Infection, and Myelokathexis). Myelokathexis refers to retention (kathexis) of neutrophils in the bone marrow (myelo). Myelokathexis causes severe chronic leukopenia and neutropenia. CXCR4 antagonist plerixafor corrects panleukopenia in patients with WHIM syndrome (http://goo.gl/Xxbyt).
(Click to enlarge the image).
IL-4 activates STAT6, which then engages the transcription factor GATA3, leading to secretion of IL-4. GATA3 is pivotal for Th2 maturation.
T-bet (also called TBX21 or T-box 21) is pivotal for Th1 maturation.
STAT4 activates the transcription factor T-bet, which induces the secretion of IFN-gamma. T-bet promotes Th1 development by direct induction of IFN-gamma and IL-12Rbeta2 chain gene transcription.
IFN-gamma acts an amplifier by binding to its receptor on Th1 cells and activating STAT1, which then engages T-bet.
T-bet inhibits IL-4, IL-5, and IL-17 secretion.
T-bet may also inhibit Th2 differentiation by preventing GATA3 from interacting with its target DNA.
Human Th subsets, figure. UpToDate, 2009.
ScienceDirect: source 1, source 2.