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Backgroud There is an unmet need for the development of new biomarkers for idiopathic inflammatory myopathy-associated interstitial lung disease (IIM-ILD). Methods Peripheral CD4+CXCR4+ T cells, stromal cell-derived factor-1 and Krebs von den Lungen-6 were measured in patients with IIM-ILD (n = 85) and controls. The relation to pulmonary functions, high-resolution CT scores, specific clinical phenotypes and survival was analysed. Cytokine-expression profiling of these CD4+CXCR4+ T cells and their co-culture with pulmonary fibroblasts were conducted. Results The peripheral percentages of CD4+CXCR4+ T cells were significantly elevated in IIM-ILD patients, and correlated with high-resolution CT score (r = 0.7136, P < 0.0001) and pulmonary function impairments, such as percentage of forced volume vital capacity (r = −0.4734, P = 0.0005). They were associated with anti-melanoma differentiation-associated gene 5 autoantibodies and the amyopathic DM phenotype. In IIM-ILD, peripheral percentages of CD4+CXCR4+ T cells ⩾30% revealed a 6-month mortality as high as 47%. These CD4+CXCR4+ T cells express high levels of IL-21 and IL-6. In vitro blockade of IL-21 signalling by neutralization of IL-21 or Janus kinase inhibitor could abolished the fibroblast proliferation. Conclusion Overall, peripheral CD4+CXCR4+ T cells appear to be a potentially valuable novel biomarker associated with the severity and prognosis of IIM-ILD. They promote pulmonary fibroblast proliferation via IL-21, which may herald future targeted treatments for this severe disease. [ABSTRACT FROM AUTHOR]

Background Correlation of CD4+ Tcm cells in the peripheral blood to disease progression in SIVmac251 infection was examined in Chinese rhesus macaques. Methods Plasma viral RNA loads were measured by a quantitative real-time reverse transcription- PCR ( qRT- PCR) assay for SIV gag. Disease progression was determined based on time of survival. Phenotyping of CD4+ T-cell subsets in the peripheral blood was longitudinally performed by flow cytometry. Results Although CD4+ T-cell decrease and low CD4+/ CD8+ T-cell ratio in the peripheral blood after SIVmac251 infection did not correlate with disease progression, CD4+ Tcm cell decrease was observed to be correlated to disease progression in the SIVmac251-infected Chinese rhesus macaques. Conclusions Our findings suggest that CD4+ Tcm cell decrease could be used as a predictive marker for defining the pathogenesis of the SIV disease and consequently HIV/ SIV vaccine efficacy in Chinese rhesus macaques. [ABSTRACT FROM AUTHOR]

A possible mechanism of susceptibility to superinfection with simian-human immunodeficiency virus (SHIV)-1157ipd3N4 was explored in twelve SHIVSF162P3-infected Chinese rhesus macaques. Based on the kinetics of viral replication for the second infecting virus following SHIV-1157ipd3N4 inoculation, the monkeys were divided into two groups: those relatively resistant to superinfection (SIR) and those relatively sensitive to superinfection (SIS). We found that superinfection-resistant macaques had high primary viremia, whereas superinfection-sensitive macaques had low primary viremia, suggesting that primary SHIVSF162P3 infection with a high viral-replication level would repress superinfection with a heterologous SHIV-1157ipd3N4. Although no correlation of protection against superinfection with virus-specific CD4+ T cell or CD8+ T cell immune responses from gut was observed prior to superinfection, superinfection susceptibility was strongly correlated with CD4+ Tcm cells from gut both prior to the second infecting virus inoculation and on day 7 after superinfection, but not with CD4+ Tem cells from gut or with CD4+ Tcm cells from peripheral blood and lymph node. These results point to the important roles of gut-derived CD4+ Tcm cells for the study of the mechanisms of protection against superinfection and the evaluation of the safety and efficacy of vaccines and therapies against acquired immune deficiency syndrome (AIDS). [ABSTRACT FROM AUTHOR]