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

^aMutations 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.