Objective To observe immunopathological changes and cellular immune response in cutaneous lesions of patients with Penicilliosis marneffei (PSM).Methods Skin specimens were resected from cutaneous lesions of 50 patients with PSM,including 30 cases positive and 20 cases negative for human immunodeficiency virus (HIV),and from the normal skin of 10 healthy human controls.Hematoxylin-eosin staining was performed to observe histopathological changes,and immunohistochemistry to determine the expression level of tumor necrosis factor (TNF)-α,interferon (IFN)-γ interleukin (IL)-2,CD4 and CD8,in these tissue samples.Results Three histological patterns were observed in the cutaneous lesions of PSM,including granulomatous reaction in 9 HIV-positive specimens,suppurative reaction in 10 HIV-positive specimens and 9 HIV-negative specimens,anergic or necrotic reaction in 20 HIV-positive specimens and 2 HIV-negative specimens.Immunostaining was negative for CD4,CD8,TNF-α,IFN-γand IL-2 in the normal control skin.Of the 30 HIV-positive specimens,3 were strongly positive,8 mediately positive,7 positive,and 12 were negative,for CD8.The expression intensity of CD8 was significantly stronger in HIV-positive specimens than in the normal control specimens (P ＜ 0.01),while no significant difference was observed for the expression of the other tested cytokines or molecules between the HIV-positive specimens and normal control specimens (all P ＞ 0.05).The HIV-negative specimens showed enhanced expression of CD4 (2 cases strongly positive,2 moderately positive,9positive,9 negative),IL-2 (1 case moderately positive,8 positive,11 negative),IFN-γ (4 cases moderately positive,7 positive,9 negative) and TNF-α (3 cases strongly positive,2 moderately positive,5 positive,10negative) compared with the normal control specimens (all P ＜ 0.05).Meanwhile,the expression intensity of CD4 and IFN-γ significantly decreased in HIV-positive skin specimens when compared to HIV-negative specimens (both P ＜ 0.05).Enhanced expressions of CD4,IFN-γ and IL-2 were observed in specimens with granulomatous reaction compared with those with anergic or necrotic reaction(all P ＜ 0.05),while the specimens with suppurative reaction showed no statistical differences in these parameters when compared to those with granulomatous reaction and anergic or necrotic reaction (all P ＞ 0.05).Conclusions The histopathological changes in cutaneous lesions are closely associated with the immune status of patients with PSM,and T-helper type 1 immune response may play a pivotal role in the defense against Penicillium marneffei infection.