scholarly journals Skewing of the CD4+ T-Cell Pool Toward Monofunctional Antigen-Specific Responses in Patients With Immune Reconstitution Inflammatory Syndrome in The Gambia

2013 ◽  
Vol 57 (4) ◽  
pp. 594-603 ◽  
Author(s):  
H. Wilson ◽  
B. C. de Jong ◽  
K. Peterson ◽  
A. Jaye ◽  
B. Kampmann ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Reconstitution Inflammatory Syndrome ◽  
Immune Reconstitution ◽  
The Gambia ◽  
Cd4 T Cell ◽  
Cell Pool ◽  
Inflammatory Syndrome

Tuberculosis (TB)-associated immune reconstitution inflammatory syndrome in TB-HIV co-infected patients in Malaysia: prevalence, risk factors, and treatment outcomes

Sexual Health ◽  
2014 ◽  
Vol 11 (6) ◽  
pp. 532 ◽  
Author(s):  
Hong Yien Tan ◽  
Yean Kong Yong ◽  
Sin How Lim ◽  
Sasheela Ponnampalavanar ◽  
Sharifah F. S. Omar ◽  
...  
Keyword(s):  
Risk Factors ◽  
T Cell ◽  
Treatment Outcomes ◽  
Immune Reconstitution Inflammatory Syndrome ◽  
Immune Reconstitution ◽  
Cd4 T Cell ◽  
Cell Recovery ◽  
Hiv Patients ◽  
Pathogen Load ◽  
Inflammatory Syndrome

Background Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is an important early complication of antiretroviral therapy (ART) in countries with high rates of endemic TB, but data from South-East Asia are incomplete. Identification of prevalence, risk factors and treatment outcomes of TB-IRIS in Malaysia was sought. Methods: A 3-year retrospective study was conducted among TB-HIV co-infected patients treated at the University of Malaya Medical Centre. Simple and adjusted logistic regressions were used to identify the predictors for TB-IRIS while Cox regression was used to assess the influence of TB-IRIS on long-term CD4 T-cell recovery. Results: One hundred and fifty-three TB-HIV patients were enrolled, of whom 106 had received both anti-TB treatment (ATT) and ART. The median (IQR) baseline CD4 T-cell count was 52 cells μL–1 (13–130 cells μL–1). Nine of 96 patients (9.4%) developed paradoxical TB-IRIS and eight developed unmasking TB-IRIS, at a median (IQR) time of 27 (12–64) and 19 (14–65) days, respectively. In adjusted logistic regression analysis, only disseminated TB was predictive of TB-IRIS [OR: 10.7 (95% CI: 1.2–94.3), P = 0.032]. Mortality rates were similar for TB-IRIS (n = 1, 5.9%) and non-TB-IRIS (n = 5, 5.7%) patients and CD4 T-cell recovery post-ART was not different between the two groups (P = 0.363). Conclusion: Disseminated TB was a strong independent predictor of TB-IRIS in Malaysian HIV-TB patients after commencing ART. This finding underscores the role of a high pathogen load in the pathogenesis of TB-IRIS; so interventions that reduce pathogen load before ART may benefit HIV patients with disseminated TB.

scholarly journals Biomarkers of CD4+ T-cell activation as risk factors for tuberculosis-associated immune reconstitution inflammatory syndrome

AIDS ◽  
2014 ◽  
Vol 28 (11) ◽  
pp. 1593-1602 ◽  
Author(s):  
Lisa A. Chakrabarti ◽  
Céline Boucherie ◽  
Florence Bugault ◽  
Marie-Christine Cumont ◽  
Caroline Roussillon ◽  
...  
Keyword(s):  
Risk Factors ◽  
T Cell ◽  
T Cell Activation ◽  
Immune Reconstitution Inflammatory Syndrome ◽  
Immune Reconstitution ◽  
Cell Activation ◽  
Cd4 T Cell ◽  
Inflammatory Syndrome

scholarly journals Selective expansion of polyfunctional pathogen-specific CD4+ T cells in HIV-1–infected patients with immune reconstitution inflammatory syndrome

Blood ◽  
2012 ◽  
Vol 119 (13) ◽  
pp. 3105-3112 ◽  
Author(s):  
Yolanda D. Mahnke ◽  
Jamieson H. Greenwald ◽  
Rebecca DerSimonian ◽  
Gregg Roby ◽  
Lis R. V. Antonelli ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Reconstitution Inflammatory Syndrome ◽  
Immune Reconstitution ◽  
T Cell Responses ◽  
Cd4 T Cell ◽  
Phenotypic Characterization ◽  
Common Mechanism ◽  
Cell Responses ◽  
Inflammatory Syndrome ◽  
Hiv 1

AbstractSince the introduction of highly active antiretroviral therapies (ART), the prognosis for HIV-1 patients has improved immensely. However, approximately 25% of patients can experience a variety of inflammatory symptoms that are collectively known as immune reconstitution inflammatory syndrome (IRIS). Studying the etiology and immunopathology of IRIS has been hampered by the fact that the symptoms and associated opportunistic infections are highly varied. We hypothesized that there is a common mechanism underlying IRIS pathogenesis and investigated a patient group with IRIS related to different pathogens. Functional and phenotypic characterization of PBMC samples was performed by polychromatic flow cytometry after in vitro stimulation with relevant antigenic preparations. In most patients, IRIS events were characterized by the robust increase of preexisting polyfunctional, highly differentiated effector CD4+ T-cell responses that specifically targeted the antigens of the underlying co-infection. T-cell responses to HIV-1 or other underlying infections were not affected and did not differ between IRIS and non-IRIS patients. These data suggest that patients with IRIS do not have a generalized T-cell dysfunction; instead, IRIS represents a dysregulated CD4+ T-cell response against residual opportunistic infection antigen. These studies were registered at www.clinical-trials.gov as NCT00557570 and NCT00286767.

scholarly journals Elevated frequencies of highly activated CD4+ T cells in HIV+ patients developing immune reconstitution inflammatory syndrome

Blood ◽  
2010 ◽  
Vol 116 (19) ◽  
pp. 3818-3827 ◽  
Author(s):  
Lis R. V. Antonelli ◽  
Yolanda Mahnke ◽  
Jessica N. Hodge ◽  
Brian O. Porter ◽  
Daniel L. Barber ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Immune Reconstitution Inflammatory Syndrome ◽  
Cd4 T Cells ◽  
Immune Reconstitution ◽  
Interferon Γ ◽  
Effector Memory ◽  
Hiv Patients ◽  
Inflammatory Syndrome

Abstract Immune reconstitution inflammatory syndrome (IRIS) is a considerable problem in the treatment of HIV-infected patients. To identify immunologic correlates of IRIS, we characterized T-cell phenotypic markers and serum cytokine levels in HIV patients with a range of different AIDS-defining illnesses, before and at regular time points after initiation of antiretroviral therapy. Patients developing IRIS episodes displayed higher frequencies of effector memory, PD-1+, HLA-DR+, and Ki67+ CD4+ T cells than patients without IRIS. Moreover, PD-1+ CD4+ T cells in IRIS patients expressed increased levels of LAG-3, CTLA-4, and ICOS and had a Th1/Th17 skewed cytokine profile upon polyclonal stimulation. Elevated PD-1 and Ki67 expression was also seen in regulatory T cells of IRIS patients. Furthermore, IRIS patients displayed higher serum interferon-γ, compared with non-IRIS patients, near the time of their IRIS events and higher serum interleukin-7 levels, suggesting that the T-cell populations are also exposed to augmented homeostatic signals. In conclusion, our findings indicate that IRIS appears to be a predominantly CD4-mediated phenomenon with reconstituting effector and regulatory T cells showing evidence of increased activation from antigenic exposure. These studies are registered online at http://clinicaltrials.gov as NCT00557570 and NCT00286767.

scholarly journals HIV-Associated Cryptococcal Immune Reconstitution Inflammatory Syndrome is Associated with Aberrant T Cell Function and Increased Cytokine Responses

2019 ◽  
Author(s):  
David B. Meya ◽  
Samuel Okurut ◽  
Godfrey Zziwa ◽  
Stephen Cose ◽  
David R. Boulware ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Opportunistic Infection ◽  
Immune Reconstitution Inflammatory Syndrome ◽  
Cryptococcal Meningitis ◽  
Immune Reconstitution ◽  
T Cell Memory ◽  
Cell Memory ◽  
Cytokine Responses ◽  
Inflammatory Syndrome

Cryptococcal meningitis remains a significant opportunistic infection among HIV-infected patients, contributing 15%-20% of HIV-related mortality. A complication of initiating Antiretroviral therapy (ART) following opportunistic infection is Immune Reconstitution Inflammatory Syndrome (IRIS). IRIS afflicts 10-30% of HIV-infected patients with cryptococcal meningitis (CM), but its immunopathogenesis is poorly understood. We compared circulating T cell memory subsets and cytokine responses among 17 HIV-infected Ugandans with CM: 11 with and 6 without CM-IRIS. At meningitis diagnosis, stimulation with cryptococcal capsule component, glucuronoxylomannan (GXM) elicited consistently lower frequencies of CD4+ and CD8+ T cell memory subsets expressing intracellular cytokines (IL-2, IFN-γ and IL-17) among subjects who subsequently developed CM-IRIS. After ART initiation, T cells evolved to show a decreased CD8+ central memory phenotype. At the onset of CM-IRIS, stimulation more frequently generated polyfunctional IL-2+/IL-17+ CD4+ T cells in patients with CM-IRIS. Moreover, CD8+ central and effector memory T cells from CM-IRIS subjects also demonstrated more robust IL-2 responses to antigenic stimulation vs. controls. Thus, ART during CM elicits distinct differences in T cell cytokine production in response to cryptococcal antigens both prior to and during the development of IRIS, suggesting an immunologic foundation for the development of this morbid complication of CM infection.

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