Recurrent Tonsillitis Tfh Cells Acquire a Killer Identity

Abstract

Group A Streptococcus (GAS) infection causes recurrent tonsillitis (RT) in some individuals. A recent study (Dan et al. Sci. Transl. Med. 2019;11:eaau3776) demonstrates that RT is associated with an impaired antibody response against a key streptococcal virulence factor. This factor, SpeA, can induce abnormal T follicular helper (Tfh) cells that are able to kill B cells.

Figure 1.. SpeA Induces Killer Germinal Center (GC) T follicular helper (Tfh) Cells that Can Impair Antibody-Mediated Immunity in Recurrent Tonsillitis (RT).

Patients with RT exhibit reduced frequencies of tonsil GC Tfh cells and anti-SpeA IgG antibodies compared with those with non-RT that mount protective GC responses against Group A streptococcus (GAS) infection. GAS SpeA, (a superantigen and virulence factor) was shown to alter the functionality of GC Tfh cells, inducing a subset of these cells to express granzyme B and perforin, killing target B cells. The mechanisms by which granzyme B⁺ GC Tfh cells are induced are unclear, but may involve interactions of SpeA with different HLA class II molecules (polymorphisms). These rare granzyme B+ killer GC Tfh cells have been proposed to kill SpeA-reactive B cells, resulting in impaired anti-SpeA antibody responses, thus leading to heightened susceptibility to recurrent GAS infections and RT [5]. Abbreviation: B_GC, germinal center B cell.