Interleukin-7 receptor expression on CD8(+) T cells is reduced in HIV infection and partially restored with effective antiretroviral therapy.

Interleukin (IL)-7 enhances CD8 T-cell proliferation and cytolytic activity. The expression of its receptor, CD127 (IL-7R alpha), may therefore be important in the immunopathogenesis of HIV disease. CD127 expression on CD8(+) T cells from HIV seronegative controls, untreated HIV-seropositive patients, and HIV-positive patients receiving antiretroviral therapy with sustained viral suppression was analyzed by flow cytometry in a cross-sectional study. Among healthy controls, 65% of CD8 cells expressed CD127 ( n = 7). This dropped to 21.6% among untreated HIV-positive patients ( n = 16), and approached normal levels (47.7%) in HIV-positive individuals on effective therapy ( n = 20). The same pattern was observed for naïve (CD45RA(+) ) and memory (CD45RO(+) ) CD8(+) T cells but changes were more extreme within the memory cell population. Duration of viral suppression was the only parameter evaluated that correlated with extent of CD127 expression in treated patients. Impairment of CTL activity in HIV disease may be caused, in part, by downregulation of IL-7 receptor expression. Improved immune function with effective antiretroviral therapy is associated with recovery of this molecule. The correlation between virologic suppression and apparent CD127 recovery suggests that essential cytokine signaling pathways may be restored with sustained inhibition of viral replication.

Granulocyte inflammatory markers and airway infection during acute exacerbation of chronic obstructive pulmonary disease.

There is increasing evidence that chronic obstructive pulmonary disease (COPD) is associated with chronic inflammation in the airways and lung parenchyma; however, little is known about the inflammatory response during acute COPD exacerbation. The objectives of this study were (1) to determine if inflammatory markers associated with neutrophilic inflammation and activation increase at times of acute COPD exacerbation relative to the clinically stable state, and (2) to determine whether the presence of acute bacterial or viral infection at the time of COPD exacerbation could be correlated with increases in sputum markers of inflammation. Induced sputum was collected from patients with COPD when they were clinically stable, during the time of an acute exacerbation, and 1 mo later. Sputum was analyzed at each time point for soluble markers associated with neutrophilic inflammation; myeloperoxidase (MPO), tumor necrosis factor-alpha (TNF-alpha), and interleukin-8 (IL-8). Serologic assays on acute and convalescent sera were performed for respiratory viruses, and induced sputum was also subject to quantitative bacterial cultures, viral cultures, and polymerase chain reaction (PCR) for detection of respiratory viruses. Fourteen of the 50 patients enrolled in the study met predetermined criteria for an acute COPD exacerbation over the 15-mo study period. TNF-alpha and IL-8 were significantly elevated in the sputum of patients during acute COPD exacerbation compared with when they were clinically stable (p = 0.01 and p = 0.05, respectively). Concentrations of these cytokines declined significantly 1 mo after the exacerbation. Three of 14 patients (21%) had confirmed bacterial or viral respiratory tract infections. Patients with documented infection did not demonstrate greater increases in sputum levels of inflammatory cytokines during exacerbations compared with patients without demonstrable infection. We conclude that markers of airway neutrophilic inflammation increase at the time of acute COPD exacerbation and then decline 1 mo later, and that this acute inflammatory response appears to occur independently of a demonstrable viral or bacterial airway infection.

Progressive human immunodeficiency virus-specific immune recovery with prolonged viral suppression.

The degree of immune recovery achievable with anti-human immunodeficiency virus (HIV) therapy remains to be established. The effects of potent antiretroviral therapy, including ritonavir and saquinavir, on immune function were studied for a prolonged period in 41 patients. After 96 weeks, 88% of patients had plasma HIV RNA levels below the limit of quantitation. There were continuous increases in CD4 lymphocyte counts and in CD4:CD8 ratios over time. About half the patients developed lymphoproliferative responses to HIV p24 antigen, and nearly all developed responses to phytohemagglutinin. This occurred in parallel with increases in interleukin-12 production and expression of CD28 on CD8 lymphocytes, despite potential antiproliferative effects of protease inhibitors. Transient increases in virus load were temporally associated with loss of proliferative responses. The improved immune function, including HIV-specific immunity in many subjects, demonstrates the potential reversibility of HIV-induced immunodeficiency and does not identify a limit to immune recovery.