The accumulation of exhausted CD4<sup>+</sup> T cells was confirmed in human CBM lesions by multiplex immunofluorescence (mIF), and the progressive development of exhaustion was recapitulated in the mouse model of <i>Fonsecaea pedrosoi</i> infection.<h4>Discussion</h4>Our findings establish CD4<sup>+</sup> T cell exhaustion as an important mechanism underlying the chronicity of chromoblastomycosis, revealing a new immunopathological perspective for this neglected disease. Here, CD4 is linked to infection.