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Pulmonary fibrosis involves various types of immune cells and soluble mediators, including TGF‐β and IL‐35, a recently identified heterodimeric cytokine that belongs to the IL‐12 cytokine family. However, the effect of regulatory IL‐35 may play an important role in fibrotic diseases. The aim of this paper is to explore the immunoregulatory role of IL‐35 in the development of fibrosis in interstitial lung disease (ILD). To gain a better understanding of this issue, the concentrations of IL‐35 and different profibrotic cytokines in fibrotic (F‐ILD) and non‐fibrotic (NF‐ILD) patients by ELISA were compared to that of intracellular IL‐35 and IL‐17 on CD4+ T cells stimulated in the presence of BAL or with different ratios of recombinant IL‐35 (rIL‐35) and TGF‐β (rTGF‐β), which were evaluated by flow cytometry. We observed that BAL concentration of IL‐35 was lower in F patients (p < 0.001) and was negatively correlated with concentrations of TGF‐β (p < 0.001) and IL‐17 (p < 0.001). In supplemented cell cultures, BAL from NF but not F patients enhanced the percentage of IL‐35 + CD4+ T (p < 0.001) cells and decreased the percentage of IL‐17 + CD4+ T cells (p < 0.001). The percentage of IL‐35 + CD4+ T cells correlated positively with BAL concentration of IL‐35 (p = 0.02), but correlated negatively with BAL concentrations of IL‐17 (p = 0.007) and TGF‐β (p = 0.01). After adjusting the concentrations of recombinant cytokines to establish a TGF‐β: IL‐35 ratio of 1:4, an enhanced percentage of IL‐35 + CD4+ T cells (p < 0.001) but a decreased percentage of IL‐17 + CD4+ T cells (p < 0.001) was observed. After adding recombinant IL‐35 to the BAL from F patients until a 1:4 ratio of TGF‐β: IL‐35 was reached, a significantly increased percentage of IL‐35 + CD4+ T cells (p < 0.001) and a decreased percentage of IL‐17 + CD4+ T cells (p = 0.003) was found. These results suggest that IL‐35 may induce an anti‐fibrotic response, regulating the effect of TGF‐β and the inflammatory response on CD4+ T cells. In addition, the TGF‐β: IL‐35 ratio in BAL has been shown to be a potential biomarker to predict the outcome of F patients with ILD. [ABSTRACT FROM AUTHOR]

Natural killer ( NK) cells provide an immediate first line of defence against viral infections. Memory responses, maintained by CD4+ T cells, require exposure to viral antigen and provide long-term protection against future infections. It is known that NK cells can promote the development of the adaptive response through cytokine production and cross-talk with antigen-presenting cells. In this paper however, we summarize a series of recent publications, in mouse models and for the first time in man, with the unifying message that rapid viral antigen control by the innate immune system limits antigen exposure to CD4+ cells thereby abrogating the development of a memory response. We discuss the significant implication of these studies on viral treatment strategies and immunization models. [ABSTRACT FROM AUTHOR]

This paper describes a model of successful immunotherapy of advanced lymphoma based on the selective elimination of cycling tumour-induced suppressor T cells. It shows that a single injection of the anti-mitotic drug, vinblasting (Vb), results in complete regression of a large L5178Y lymphoma and its metastases, but not if it is growing in an immunocompetent host. Vb-induced, immunologically mediated tumour regression was dependent on the anti-tumour function of CD8+ T cells, because regression was prevented by depleting the host of this subset of T cells 24 hr after Vb was given. Regression was also prevented by infusing the host with Vb-sensitive, CD4+ T cells from a turnout-bearing donor. These and other results are in keeping with the interpretation that Vbinduced regression of the L5178Y lymphoma depends on the ability of the drug to eliminate CD4+ suppressor T ceils that are replicating, and to spare non-replicating CD8+ effector cells, it is suggested that at an advanced stage of growth of the L5178Y lymphoma the host possesses an acquired population of antigen-primed CD8+ effector T cells that are unable to become activated in response to abundant tumour antigen because of the dominant influence of CD4+ suppressor cells. Activation of these CD8+ T cells was indicated by the finding that they were rapidly converted from being cyclophosphamide (Cy) resistant to being highly Cy sensitive within 48 hr of giving Vb. [ABSTRACT FROM AUTHOR]

The leucocyte common antigen, CD45 (T200, Ly-5), exists in a number of isoforms generated by differential usage of three exons that code for an extracellular region close to the NH2 terminus. Use of antibodies to different isoforms of CD45 has lead to the identification of two subsets of CD4+ T cells in rat, man and mouse. Data on the functions of the two rat CD4+ T-cell subsets isolated on the basis of different levels of expression of exon B (and/or C) are largely concordant with those obtained from the two subsets of human CD4 + T cells defined by their levels of expression of exon A. However, results presented in this paper on the CD45 phenotype of rat T cells that produce interferon-gamma (IFN-γ) are not compatible with the human data, if it is assumed that there are only two functional subsets of CD4+ T cells. The data could, in principle, be reconciled if the expression of exons A and B defined three rather than two subsets, and this possibility has now been examined in man where monoclonal antibodies against both A and B exon products are available. The results show the presence of a third CD4+ T-cell subset and that this extra subset is contained within the population originally shown to provide memory T-cell function. [ABSTRACT FROM AUTHOR]