CD4 and rheumatoid arthritis: In addition to Tfh cells in secondary lymphoid tissues, other CD4+ T cells in peripheral tissues contribute to B-cell activation and antibody production; these cells are known as Tph cells.223 Tph cells were originally identified in rheumatoid arthritis and shown to express the Tfh hallmarks IL-21, ICOS, c-Maf, and high levels of PD-1.224 However, unlike Tfh cells, Tph cells express low levels of Bcl-6 and do not express CXCR5, which makes Tph cells a specific CD4+ T-cell subset.224