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Table 1.

Effects of gene deficiency on Tfh cell formation and identification of regulators of Tfh formation

Gene/protein Effect of KO on Tfh cells References 
Cytokines   
IL-6 Mild/moderate decrease/no effect Nurieva et al., 2008; Poholek et al., 2010; Eto et al., 2011; Harker et al., 2011  
IL-21, IL-21R Mild/moderate decrease/no effect Vogelzang et al., 2008; Linterman et al., 2010; Poholek et al., 2010; Eto et al., 2011  
IL-27Ra Decreased Batten et al., 2010  
Signaling   
SH2D1A (SAP)a Absent Qi et al., 2008; Linterman et al., 2009; Cannons et al., 2010; Deenick et al., 2010  
STAT3a Decreased Nurieva et al., 2008; Lu et al., 2011  
STAT5 Increased Johnston et al., 2012  
Transcription factors   
Bcl-6 Absent Johnston et al., 2009; Nurieva et al., 2009; Yu et al., 2009; Poholek et al., 2010  
c-Maf Decreased Bauquet et al., 2009; Pot et al., 2009; Hiramatsu et al., 2010; Kroenke et al., 2012  
BATF Absent Betz et al., 2010; Ise et al., 2011  
IRF4 Decreased/absent Kwon et al., 2009  
PRDM1 (Blimp1) Increased Johnston et al., 2009  
Tbx21 (T-bet) Increased Nakayamada et al., 2011; Oestreich et al., 2012  
Surface receptors   
CD40/CD40La Decreased/absent Akiba et al., 2005; Bossaller et al., 2006  
ICOSa/ICOS-L Decreased/absent 
CD28 Decreased/absent Akiba et al., 2005; Salek-Ardakani et al., 2011  
CD80 No effect 
CD86 Decreased  
CD84 Decreased Cannons et al., 2010  
Gene/protein Effect of KO on Tfh cells References 
Cytokines   
IL-6 Mild/moderate decrease/no effect Nurieva et al., 2008; Poholek et al., 2010; Eto et al., 2011; Harker et al., 2011  
IL-21, IL-21R Mild/moderate decrease/no effect Vogelzang et al., 2008; Linterman et al., 2010; Poholek et al., 2010; Eto et al., 2011  
IL-27Ra Decreased Batten et al., 2010  
Signaling   
SH2D1A (SAP)a Absent Qi et al., 2008; Linterman et al., 2009; Cannons et al., 2010; Deenick et al., 2010  
STAT3a Decreased Nurieva et al., 2008; Lu et al., 2011  
STAT5 Increased Johnston et al., 2012  
Transcription factors   
Bcl-6 Absent Johnston et al., 2009; Nurieva et al., 2009; Yu et al., 2009; Poholek et al., 2010  
c-Maf Decreased Bauquet et al., 2009; Pot et al., 2009; Hiramatsu et al., 2010; Kroenke et al., 2012  
BATF Absent Betz et al., 2010; Ise et al., 2011  
IRF4 Decreased/absent Kwon et al., 2009  
PRDM1 (Blimp1) Increased Johnston et al., 2009  
Tbx21 (T-bet) Increased Nakayamada et al., 2011; Oestreich et al., 2012  
Surface receptors   
CD40/CD40La Decreased/absent Akiba et al., 2005; Bossaller et al., 2006  
ICOSa/ICOS-L Decreased/absent 
CD28 Decreased/absent Akiba et al., 2005; Salek-Ardakani et al., 2011  
CD80 No effect 
CD86 Decreased  
CD84 Decreased Cannons et al., 2010  
a

Mutations in STAT3, CD40L, and ICOS in humans results in reduced frequencies of circulating CD4+CXCR5+ T cells in the peripheral blood (Bossaller et al., 2006; Ma et al., 2012), while mutations in SH2D1A compromise Tfh-like function of CD4+ T cells (Ma et al., 2005). These mutations are associated with impaired humoral immune responses in affected individuals.

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