Follicular B Helper T cells

Follicular B helper T cells (also known as just Follicular helper T cells or TFH), are antigen-experienced CD4+ T cells found in the B cell follicles of secondary lymphoid organs such as lymph nodes, spleens and Peyer's patches, and are identified by their constitutive expression of the B cell follicle homing receptor CXCR5[1]. TFH cells are found within B cell follicles and mediate antigen specific naïve or memory B cell activation, which triggers germinal center formation, probably through the expression of CD40L and the secretion of IL-21[2] and IL-4[3]. It is possible that TFH cells might arise as branches in the Th1 and Th2 differentiation pathways but their precise lineage relationship to the other effector CD4+ T cell subsets is still uncertain. Recent studies have however shown that TFH have distinct gene expression profiles, supporting the theory that TFH are a subset of CD4+ T cells distinct from Th-1, Th-2, Th-17 or Tregs[4][5].

Role of ICOS

The Inducible T-cell co-stimulator (CD278 or ICOS) has proven to provide a particularly critical signal for TFH cells since mice deficient in ICOS are unable to develop any TFH[6], although the exact mechanisms involved are as of yet unknown[7]. However, it was shown that ICOS induces the secretion of IL-21 by activated CD4+ T cells and that IL-21 plays a crucial role in the development of TFH[8][9]. Also Bcl-6 is a transcription factor identified in TFH cells, but it may have roles that extend beyond this subset, because it has been implicated in memory CD8+ T cell development.[10].

Autoimmunity

Finally, it has been shown that dysregulated TFH cells can cause systemic autoimmunity and auto-antibody production or contribute to T cell–mediated organ-specific autoimmunity.[7]

References

  1. ^ Fazilleau et al.; Mark, L; McHeyzer-Williams, LJ; McHeyzer-Williams, MG (March 2009). "Follicular helper T cells: lineage and location". Immunity 30 (3): 324–35. doi:10.1016/j.immuni.2009.03.003. PMC 2731675. PMID 19303387. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2731675. 
  2. ^ Seo et al.; Youn, J; Kim, PH (May 2009). "IL-21 ensures TGF-beta 1-induced IgA isotype expression in mouse Peyer's patches". J Leukoc Biol 85 (5): 744–50. doi:10.1189/jlb.0708450. PMID 19168593. 
  3. ^ Zaretsky et al.; Taylor, JJ; King, IL; Marshall, FA; Mohrs, M; Pearce, EJ (May 2009). "T follicular helper cells differentiate from Th2 cells in response to helminth antigens". J Exp Med 206 (5): 991–9. doi:10.1084/jem.20090303. PMC 2715032. PMID 19380637. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2715032. 
  4. ^ Chtanova et al.; Tangye, SG; Newton, R; Frank, N; Hodge, MR; Rolph, MS; MacKay, CR (July 2004). "T follicular helper cells express a distinctive transcriptional profile, reflecting their role as non-Th1/Th2 effector cells that provide help for B cells". J Immunol 173 (1): 68–78. PMID 15210760. 
  5. ^ Nurieve et al.; Chung, Y; Hwang, D; Yang, XO; Kang, HS; Ma, L; Wang, YH; Watowich, SS et al. (July 2008). "Generation of T follicular helper cells is mediated by interleukin-21 but independent of T helper 1, 2, or 17 cell lineages". Immunity 29 (1): 138–49. doi:10.1016/j.immuni.2008.05.009. PMC 2556461. PMID 18599325. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2556461. 
  6. ^ Akiba; Takeda, K; Kojima, Y; Usui, Y; Harada, N; Yamazaki, T; Ma, J; Tezuka, K et al. (Aug 2005). "The role of ICOS in the CXCR5+ follicular B helper T cell maintenance in vivo". J Immunol 175 (4): 2340–8. PMID 16081804. 
  7. ^ a b Vinuesa et al.; Cook, MC; Angelucci, C; Athanasopoulos, V; Rui, L; Hill, KM; Yu, D; Domaschenz, H et al. (May 2005). "A RING-type ubiquitin ligase family member required to repress follicular helper T cells and autoimmunity". Nature 435 (7041): 452–8. doi:10.1038/nature03555. PMID 15917799. 
  8. ^ Bauquet; Jin, H; Paterson, AM; Mitsdoerffer, M; Ho, IC; Sharpe, AH; Kuchroo, VK (Feb 2009). "The costimulatory molecule ICOS regulates the expression of c-Maf and IL-21 in the development of follicular T helper cells and TH-17 cells". Nat Immunol 10 (2): 167–75. doi:10.1038/ni.1690. PMC 2742982. PMID 19098919. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2742982. 
  9. ^ Vogelzang; McGuire, HM; Yu, D; Sprent, J; MacKay, CR; King, C (July 2008). "A fundamental role for interleukin-21 in the generation of T follicular helper cells". Immunity 29 (1): 127–37. doi:10.1016/j.immuni.2008.06.001. PMID 18602282. 
  10. ^ Ichii et al.; Sakamoto, A; Hatano, M; Okada, S; Toyama, H; Taki, S; Arima, M; Kuroda, Y et al. (June 2002). "Role for Bcl-6 in the generation and maintenance of memory CD8+ T cells". Nat Immunol 3 (6): 558–63. doi:10.1038/ni802. PMID 12021781. 
Myeloid lineage - Blood (WBC and RBC)
Cellular/
HSCs
Common
Noncellular

M: MYL

cell/phys (coag, heme, immu, gran), csfs

rbmg/mogr/tumr/hist, sysi/epon, btst

drug (B1/2/3+5+6), btst, trns