RESUMO
Although CD4(+) T cells are known to contribute to the pathology of atopic dermatitis (AD) and psoriasis, the role of CD8(+) T cells in these diseases remains poorly characterized. The aim of this study was to characterize the cytokine production of T cells from AD and psoriasis skin. We found that CD4(+) T cells isolated from AD skin were largely Th2 (T helper type 2) biased, in agreement with prior reports. However, we also observed large numbers of CD8(+) T cells producing IL-13, IFN-γ, and IL-22. We observed increased numbers of CD8(+) T cells isolated from AD skin, and immunohistochemistry studies confirmed the presence of CD8(+) T cells in the dermis and epidermis of AD skin lesions. Surprisingly, T-cell cytokine production was similar in the lesional and nonlesional skin of patients with AD. T cells from psoriatic lesional skin predominantly produced IFN-γ, IL-17, and IL-22, in agreement with prior studies. However, in addition to Th17 cells, we observed high percentages of CD8(+) T cells that produced both IL-22 and IL-17 in psoriatic skin lesions. Our findings demonstrate that CD8(+) T cells are a significant and previously unappreciated source of inflammatory cytokine production in both AD and psoriasis.
Assuntos
Linfócitos T CD8-Positivos/imunologia , Dermatite Atópica/imunologia , Interferon gama/imunologia , Interleucina-13/imunologia , Interleucina-17/imunologia , Interleucinas/imunologia , Psoríase/imunologia , Adulto , Idoso , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/patologia , Polaridade Celular/imunologia , Células Cultivadas , Dermatite Atópica/metabolismo , Dermatite Atópica/patologia , Humanos , Interferon gama/metabolismo , Interleucina-13/metabolismo , Interleucina-17/metabolismo , Interleucinas/metabolismo , Pessoa de Meia-Idade , Psoríase/metabolismo , Psoríase/patologia , Células Th1/imunologia , Células Th1/metabolismo , Células Th1/patologia , Células Th2/imunologia , Células Th2/metabolismo , Células Th2/patologia , Adulto Jovem , Interleucina 22RESUMO
Chronic graft-versus-host disease is the major long-term complication after allogeneic stem cell transplantation with a suboptimal response rate to current treatments. Therefore, clinical efficacy and changes in lymphocyte subsets before and after rituximab treatment were evaluated in a prospective phase II study in patients with steroid-refractory chronic graft-versus-host disease. Overall response rate was 61%. Only responding patients were found to have increased B-cell numbers prior to treatment. B cells had a naïve-antigen-presenting phenotype and were mainly CD5 negative or had a low CD5 expression. Normal B-cell homeostasis was reestablished in responding patients one year after ritxumab treatment and associated with a significant decline in skin-infiltrating CD8(+) T cells, suggesting that host B cells play a role in maintaining pathological CD8(+) T-cell responses. Imbalances in B-cell homeostasis could be used to identify patients a priori with a higher chance of response to rituximab treatment (Eudra-CT 2008-004125-42).
