Lung HIV-specific CD4+ T cells from a representative HIV+COPD+ subject exhibit diminished multifunctional capacity compared with an HIV+COPD? individual (Figure 3A). functional exhaustion. Moreover, lung CD4+ T cells from HIV+COPD+ patients demonstrated increased basal and HIV antigen-induced expression of the early apoptosis marker annexin V compared with control subjects, which was significantly attenuated with anti-Fas blockade. Lastly, lung mucosal, but not blood, CD4+/CD8+ ratios from HIV+ patients significantly correlated with the FEV1, but not in HIV?COPD+ patients. Conclusions: Together, our results provide evidence for profound lung mucosal CD4+ T-cell depletion via a Fas-dependent activation-induced cell death mechanism, along with impaired HIV-specific CD4+ immunity as immunologic features of HIV-associated COPD. value of less than 0.05 was used to determine statistical significance. For additional details, the online supplement. Results Markedly Decreased CD4+/CD8+ Lung T-Cell Percentage and Lung Mucosal CD4+ T-Cell Figures in HIV-associated COPD We evaluated T-cell immunity in an inner-city cohort of 27 HIV-infected individuals comprised of 14 HIV+COPD+, 13 HIV+COPD?, and 7 HIV?COPD+ subject matter, whose clinical characteristics are shown (Table 1). Despite related cigarette smoke exposure, HIV+COPD+ individuals shown significantly reduced FEV1% expected ideals and FEV1/FVC ratios compared with HIV+COPD? control subjects. Notably, there were no significant variations between plasma HIV viral lots, antiretroviral utilization, or peripheral CD4+ T-cell counts between the HIV+ groups. Table 1. Clinical Characteristics of Study Cohort value versus HIV+COPD? participants: *< 0.001, ?< 0.01. ?Among detectable viral weight. We evaluated BAL-derived LMNC and PBMC CD4+/CD8+ T-cell ratios from HIV+COPD+, HIV+COPD?, or HIV?COPD+ individuals using circulation cytometry. LMNC CD4+/CD8+ ratios were significantly decreased in HIV+COPD+ versus HIV+COPD? and HIV?COPD+ individuals (Numbers 1A and 1B). In contrast, there was no difference in PBMC CD4+/CD8+ ratios between HIV+ organizations (Numbers 1D and 1E). Open in a separate window Number 1. Marked depletion of lung mucosal CD4+ T cells in HIV-associated chronic obstructive pulmonary disease (COPD). (indicate frequencies of CD4+ or CD8+ T-cell populations. Plots are representative of 34 LMNC RAD26 analyzed from individuals during chronic HIV illness (14 COPD+, 13 COPD?, and 7 HIV?COPD+). (ideals were determined using the Wilcoxon authorized rank test or the Mann-Whitney test. Next, we identified whether TAS 301 the absolute quantity of lung mucosal CD4+ T cells differed. We observed a significant reduction in LMNC CD4+ T-cell complete figures in HIV+COPD+ individuals, but no difference in complete CD8+ T cells (Number TAS 301 1C). Interestingly, decreased absolute BAL CD4+ T-cell figures/volume were TAS 301 recognized despite significantly lower total BAL volume yields in HIV+COPD+ subjects (restimulation with pooled overlapping 15-mer Pol TAS 301 peptides. (restimulation with pooled overlapping 15-mer Gag peptides. (symbolize mean values. ideals were determined using the Wilcoxon authorized rank test or the Mann-Whitney test. Next, we evaluated the multifunctional capacity of effector function in HIV-specific CD4+ memory space T cells in LMNC and PBMC for IFN-, TNF-, IL-2, CD107 mobilization, and MIP-1. Lung HIV-specific CD4+ T cells from a representative HIV+COPD+ subject exhibit diminished multifunctional capacity compared with an HIV+COPD? individual (Number 3A). Using Boolean analysis, we identified the percentage of individual multifunctional reactions between HIV+COPD+ and HIV+COPD? individuals for LMNC and PBMC and found that LMNC from HIV+COPD+ shown decreased frequencies of Pol- and Gag-specific (= 0.03; data not shown) CD4+ T cells generating 2+, 3+, or 4+ cytokines and chemokines in contrast to CD4+ T cells from HIV+COPD? individuals (Number 3B). Open in a separate window Number 3. Loss of multifunctional HIV-specific CD4+ T-cell memory space in the lung mucosa in HIV-associated chronic obstructive pulmonary disease (COPD). (and 0.05, **0.001..
Lung HIV-specific CD4+ T cells from a representative HIV+COPD+ subject exhibit diminished multifunctional capacity compared with an HIV+COPD? individual (Figure 3A)