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Allergic asthma is a chronic inflammatory T helper 2 (Th2)-associated disease. There is evidence that the atopic milieu affects the development of CD8(+) T cells in patients. We therefore analysed activation and differentiation states of CD8(+) T cells in asymptomatic patients regarding the cytomegalovirus serological status. Memory CD8(+) T cells (CCR5(high)CD3(+)CD8(+)), memory/effector cells (CD27(+)CD28(-)CD3(+)CD8(+)), effector cells (CD27(-)CD28(-)CD3(+)CD8(+)) and activated CD8(+) T cells (CD11b(+)CD3(+)CD8(+)) were identified by flow cytometry in peripheral blood of 19 (seven cytomegalovirus (CMV)(+)/12 CMV(-)) patients with allergic asthma (AA) and 21 (seven CMV(+)/14 CMV(-)) healthy controls (HC). Effector and activated CD8(+) T cells were significantly elevated in CMV(+) HC compared to CMV(-) HC. There was a non-significant trend for reduced percentages of effector CD8(+) T cells in CMV(+) AA (median: 10.4%, range: 4.4-33.8%) compared to CMV(+) HC (median: 23.1%, range: 10.7-54.1%; P = 0.128) and in CMV(-) AA (median: 4.1%, range: 0.6-13.4%) compared to CMV(-) HC (median: 5.7%, range: 0.2-17.0%; P = 0.085). Activated CD8(+) T cells were reduced significantly in CMV(+) AA (median: 17.0%, range: 6.0-29.4%) compared to CMV(+) HC (median: 40.4%, range: 18.9-67.0%; P = 0.004) and showed a non-significant trend in CMV(-) AA (median: 15.0%, range: 2.9-24.0%) compared to CMV(-) HC (median: 20.2%, range: 5.8-71.0%; P = 0.060). Activated CD8(+) T cells are significantly reduced in CMV(+) patients with allergic asthma. Furthermore, a trend for an impaired terminal CD8(+) T cell differentiation is observed in CMV(+) and CMV(-) patients with asthma.

SUMMARYKiller-specific secretory protein of 37 kDa (Ksp37), identified as a Th1/Tc1 specific secretory protein is expressed preferentially in cytotoxic T lymphocytes (CTL) and natural killer (NK) cells and might be involved in essential processes of CTL-mediated immunity. Although extrinsic asthma is linked currently to a Th2-dominated pathogenesis, there is increasing evidence for Th1/Tc1-mediated processes in the aetiopathology of asthma. CTL from patients with asthma have been shown to express cytokines and effector molecules which were different from healthy controls. We hypothesized that Ksp37 could indicate the involvement of CTL in the pathogenesis of extrinsic asthma. We therefore investigated Ksp37 expression in PBMC from patients with mild extrinsic asthma (n = 7) and healthy controls (n = 7). Flow cytometric analysis was used to quantify Ksp37+ cells and to investigate cellular Ksp37 expression as relative mean fluorescence intensities (MFI). We found a significantly (P = 0·016) higher percentage of Ksp37+ cells within the total lymphocyte population obtained from patients with mild extrinsic asthma compared with healthy controls. Subdifferentiation revealed a significant difference limited exclusively to the CD8+ subset (P = 0·010). In addition, Ksp37 secretion from cultured peripheral blood mononuclear cells (PBMC) and MFI of Ksp37+ lymphocytes were increased in patients with asthma compared with healthy controls. We conclude that mild extrinsic asthma appears to be associated with an increased expression of the Tc1 related protein Ksp37. The functional role of Ksp37 in the pathogenesis of asthma remains to be elucidated.

SUMMARYAsthma has been linked to a chronic, T-cell-mediated bronchial inflammation. Because other T-lymphocyte-mediated, chronic inflammatory disorders have been associated with elevated granzyme B (grB) expression we tested the hypothesis that atopic asthma might be associated with elevated grB levels in the bronchoalveolar compartment. Therefore we performed intracellular grB staining in lymphocytes from bronchoalveolar lavage (BAL) collected 42 h after segmental allergen provocation (SAP) in allergic patients with bronchial asthma. There was a significant increase in CD3+, CD8+, and CD16/56+ lymphocytes expressing grB in BAL 42 h after SAP as compared to saline challenged controls. However, compared to peripheral blood the percentages of these lymphocyte subsets detected as grB+ in BAL remained significantly lower. Measurement of extracellular grB in BAL fluids by a particle immunoassay revealed significantly elevated grB levels in the allergen challenged bronchoalveolar compartment 42 h following SAP in six of the eight patients (range

SummaryIt has been postulated that T lymphocytes orchestrate the chronic inflammation in bronchial asthma. In animal models, infiltration of CD8+ T lymphocytes into the bronchial mucosa prevented bronchial hyperresponsiveness and decreased early and late phase reaction. IFN-γ antagonizes IL-4-dependent IgE production as well as IL-5-induced proliferation and activation of eosinophils. We therefore investigated the secretion of IFN-γ of isolated CD8+ T lymphocytes from peripheral blood of patients with allergic asthma (n = 6) and from healthy controls (n = 7) in vitro. In this setting we compared the effect of stimulation with anti-CD3 antibodies with that of phorbol myristate acetate (PMA) and calcium-ionophore. As expected, CD8+ T lymphocytes from peripheral blood of healthy volunteers produced significantly more IFN-γ in the presence of PMA and calcium-ionophore than after stimulation with anti-CD3 antibodies. However, in subjects with allergic asthma, IFN-γ secretion of CD8+ T cells was significantly higher when incubated with anti-CD3 antibodies than after activation with PMA and calcium-ionophore. While IFN-γ secretion of CD8+ T lymphocytes of patients with allergic asthma was lower than that of healthy controls in the presence of PMA/calcium-ionophore, it was significantly elevated when compared with normal controls after stimulation with anti-CD3 antibodies. Thus, potent activators of cytokine secretion, such as PMA and calcium-ionophore, induce a cytokine profile different from that induced by weaker stimulants, such as anti-CD3 antibodies. These findings have implications for further studies investigating cytokine production of inflammatory cells in vitro.