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 |
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.