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Memory T cells play a central role in regulating inflammatory responses during asthma. However, tissue distribution of effector memory (TEM) and central memory (TCM) T-cell subtypes, their differentiation, and their contribution to the persistence of lung tissue inflammation during asthma are not well understood. Interestingly, an increase in survival and persistence of memory T cells was reported in asthmatic lungs, which may suggest a shift toward the more persistent TCM phenotype. In this report, we investigated the differential distribution of memory T-cell subtypes during allergic lung inflammation and the mechanism regulating that. Using an OVA-sensitized asthma mouse model, we observed a significant increase in the frequency of TCM cells in inflamed lungs compared to healthy controls. Interestingly, adoptive transfer techniques confirmed substantial infiltration of TCM cells to lung tissues during allergic airway inflammation. Expression levels of TCM homing receptors, CD34 and GlyCAM-1, were also significantly upregulated in the lung tissues of OVA-sensitized mice, which may facilitate the increased TCM infiltration into inflamed lungs. Moreover, a substantial increase in the relative expression of TCM profile-associated genes (EOMES, BCL-6, ID3, TCF-7, BCL-2, BIM, and BMI-1) was noted for TEM cells during lung inflammation, suggesting a shift for TEM into the TCM state. To our knowledge, this is the first study to report an increased infiltration of TCM cells into inflamed lung tissues and to suggest differentiation of TEM to TCM cells in these tissues. Therapeutic interference at TCM infiltration or differentiations could constitute an alternative treatment approach for lung inflammation. [ABSTRACT FROM AUTHOR]

Inhaled glucocorticoid therapy may improve symptoms of asthma in children by reducing activated peripheral blood T cells and mRNA expression of immune protein. Researchers measured levels of peripheral blood mononuclear cells (PBMC) from 17 children with asthma and from seven nonasthmatic children. Children with more severe asthma had higher levels of activated peripheral T cells and greater expression of certain activation markers than did children with milder asthma. Asthmatic children needed increasingly larger doses of inhaled glucocorticoid therapy to control symptoms over the six month study period., Objective. To investigate the role of activated T cells and their cytokine products in the pathogenesis of childhood asthma. Methods. PBMC were obtained from 17 symptomatic asthmatic children (age 7 to 15 yr) and 7 nonasthmatic controls matched for age and atopic status. Asthmatics were placed in 2 groups with initial prebronchodilator [FEV.sub.1] [is less than] 75% (Group I, n = 9) or [is greater than or equal to] 75% (Group II, n = 8) predicted. Expression of activation markers on peripheral blood T cells (asthmatics), and expression of cytokine mRNA (asthmatics and controls) were measured using flow cytometry and in situ hybridization respectively. Measurements were repeated in the asthmatics 3 to 6 months later following initiation or escalation of inhaled GC therapy for control of symptoms. Results. The more severe (Group I) as compared with the milder (Group II) asthmatics showed evidence of increased peripheral blood T cell activation, with elevated percentages of CD4 cells expressing the activation markers CD25 and HLA-DR, and CD8 cells expressing CD25. Elevated percentages of CD4 cells also expressed CD45RO, consistent with ongoing cellular activation. The asthmatics had higher percentages of PBMC expressing mRNA encoding IL-5, IL-4, GM-CSF and IL-2, but not IFN-[Gamma], as compared with controls. The percentages of PBMC expressing IL-5 mRNA correlated with disease severity (% predicted [FEV.sub.1]). During follow up, patients in both groups required increased mean daily dosages of inhaled GC. In Group I this was associated with improvements in PEFR, [FEV.sub.1] and night time wheeze and reduced percentages of CD4/CD25 and CD4/HLA-DR peripheral blood T cells. Reductions in the percentages of CD4/CD25 T cells correlated with improvements in baseline [FEV.sub.1]. Group II patients showed improvement in [FEV.sub.1] and day time cough and wheeze but no significant changes in PEFR, other symptoms or peripheral blood T cell marker expression. Increased GC therapy of both groups taken together was associated with significant reductions in the percentages of PBMC expressing mRNA encoding IL-5, IL-4 and IL-2 and an increase in those expressing IFN-[Gamma] mRNA. Conclusions. Compared with controls, children with symptomatic asthma have higher percentages of activated peripheral blood T cells synthesising cytokines believed to regulate bronchial mucosal eosinophilic inflammation. Clinical improvement with increased inhaled GC therapy is associated with reduced T cell activation and cytokine mRNA expression. Pediatrics 1997; 99:695-703; asthma, child, T lymphocyte, cytokine, glucocorticoid., ABBREVIATIONS. IL, interleukin; GM-CSF, granulocyte/macrophage colony stimulating factor; GC, glucocorticoid; IFN-[Gamma], interferon gamma; mRNA, messenger ribonucleic acid; BAL, bronchoalveolar ravage; [FEV.sub.1], forced expiratory volume in 1 second; PBMC, peripheral blood [...]