CD9 identifies and regulates a highly functional and unique subset of T follicular helper (Tfh) cells necessary for the promotion of antibodies during infection

Abstract T follicular helper (Tfh) cells comprise a subset of CD4 +T (Th) phenotypically and functionally distinct from Th1 Th2 cell subsets. Tfh are located within B follicles germinal centers (GC), where they secrete the cytokines IL-21 interferon-γ (IFN-γ) which aid in proliferation differentiation. CD9, tetraspanin, has been shown to accumulate on at immunological synapse, playing role co-stimulation stabilization synapse via regulation integrins LFA-1 VLA-4. CD9 be expressed activated cells, but whether it remains upregulated specifically is unknown. We identified population CD9-expressing (CD9 hi) following acute viral infections examined their promoting GC responses. Following LCMV infection, hiTfh found GCs, yet exhibited enhanced migratory capacity chemokines CXCL12 CXCL13. Epigenetically, demonstrated transcriptional profile chromatin architecture locounterpart, with an upregulation cycling, PI3K, integrin-regulated genes. Functionally, had elevated VLA-4 expression were predominant producers IFN-γ, indicating specific maturation Furthermore, deletion did not alter development, lead reduction IFN-γ production decrease overall antibody Therefore, we that highly functional unique necessary for promotion antibodies during infection. R01 AR073912