28 research outputs found
Impact of HIV on CD8+ T Cell CD57 Expression Is Distinct from That of CMV and Aging
Background: Chronic antigenic stimulation by cytomegalovirus (CMV) is thought to increase ‘‘immunosenesence’’ of aging, characterized by accumulation of terminally differentiated CD28- CD8+ T cells and increased CD57, a marker of proliferative history. Whether chronic HIV infection causes similar effects is currently unclear.
Methods: We compared markers of CD8+ T cell differentiation (e.g., CD28, CD27, CCR7, CD45RA) and CD57 expression on CD28- CD8+ T cells in healthy HIV-uninfected adults with and without CMV infection and in both untreated and antiretroviral therapy (ART)-suppressed HIV-infected adults with asymptomatic CMV infection.
Results: Compared to HIV-uninfected adults without CMV (n = 12), those with asymptomatic CMV infection (n = 31) had a higher proportion of CD28-CD8+ T cells expressing CD57 (P = 0.005). Older age was also associated with greater proportions of CD28-CD8+ T cells expressing CD57 (rho: 0.47, P = 0.007). In contrast, untreated HIV-infected CMV+ participants (n = 55) had much lower proportions of CD28- CD8+ cells expressing CD57 than HIV-uninfected CMV+ participants (P,0.0001) and were enriched for less well-differentiated CD28- transitional memory (TTR) CD8+ T cells (P,0.0001). Chronically HIV-infected adults maintaining ART-mediated viral suppression (n = 96) had higher proportions of CD28-CD8+ T cells expressing CD57 than untreated patients (P,0.0001), but continued to have significantly lower levels than HIV-uninfected controls (P = 0.001). Among 45 HIV-infected individuals initiating their first ART regimen, the proportion of CD28-CD8+ T cells expressing CD57 declined (P,0.0001), which correlated with a decline in percent of transitional memory CD8+ T cells, and appeared to be largely explained by a decline in CD28-CD57- CD8+ T cell counts rather than an expansion of CD28-CD57+ CD8+ T cell counts.
Conclusions: Unlike CMV and aging, which are associated with terminal differentiation and proliferation of effector memory CD8+ T cells, HIV inhibits this process, expanding less well-differentiated CD28- CD8+ T cells and decreasing the proportion of CD28- CD8+ T cells that express CD57
Statistical Modeling of D- and z-value of E. coli O157:H7 and pH in Apple Cider Containing Preservatives
Ethnological and clinical considerations on the relationship between body weight and arteriosclerosis
Interpretation and Use of the Western Blot Assay for Serodiagnosis of Human Immunodeficiency Virus Type 1 Infections
CHARACTERIZATION OF NORMAL AND ABNORMAL CANINE SUPERFICIAL LYMPH NODES USING GRAY-SCALE B-MODE, COLOR FLOW MAPPING, POWER, AND SPECTRAL DOPPLER ULTRASONOGRAPHY: A MULTIVARIATE STUDY
The immunological footprint of CMV in HIV-1 patients stable on long-term ART
BACKGROUND:Most HIV-infected persons are cytomegalovirus (CMV) seropositive and retain latent virus that can be reactivated by immune activation. Their T cell populations express markers reflecting a late stage of differentiation, but the contributions of HIV and CMV to this profile are unclear. We investigated the immunological "footprint" of CMV in HIV patients who had a history of extreme immunodeficiency but were now stable on antiretroviral therapy (ART).RESULTS:Twenty CMV seropositive HIV patients >50years old with nadir CD4 T-cell counts <200 cells/mul were studied after >12years on ART. 16 CMV seropositive and 9 CMV seronegative healthy controls were included. CMV antibody titres were higher in HIV patients than controls (P<0.001-0.003). Levels of soluble B-cell activating factor (sBAFF) were elevated in patients (P=0.002) and correlated with levels of CMV antibodies (P=0.03-0.002), with no clear relationship in controls. CD8 T-cell IFNgamma responses to the IE1 peptide (VLE) remained elevated in HIV patients (P=0.005). The CD57 + CD45RA + CD27 phenotype of CD8 T-cells correlated with age (r=0.60, P=0.006), antibodies against CMV IE1 protein (r=0.44, P=0.06) and CD4 T-cell IFNgamma response to CMV lysate (r=0.45, P=0.05).CONCLUSIONS:Humoral and T-cell responses to CMV remained elevated in HIV patients after >12years on ART. Age and presence of CMV disease influenced CD8 T-cell phenotypes. Elevated levels of sBAFF may be a consequence of HIV disease and contribute to high titres of CMV antibody