Browsing by Subject "CD4"

Now showing 1 - 5 of 5
  • Thumbnail Image
    Item
    Bone Mineral Density in Children and Adolescents with Perinatal HIV Infection
    (Wolters Kluwer, 2013) Dimeglio, Linda A.; Wang, JiaJia; Siberry, George K.; Miller, Tracie L.; Geffner, Mitchell E.; Hazra, Rohan; Borkowsky, William; Chen, Janet S.; Dooley, Laurie; Patel, Kunjal; Van Dyke, Russell B.; Fielding, Roger A.; Gurmu, Yared; Jacobson, Denise L.; Pediatric HIV/AIDS Cohort Study; Pediatrics, School of Medicine
    Objective: To estimate prevalence of low bone mineral density (BMD) in perinatally HIV-infected (HIV+) and HIV-exposed but uninfected (HEU) children, and to determine predictors of BMD in HIV+. Design: Cross-sectional analysis within a 15-site United States and Puerto Rico cohort study. Methods: Total body and lumbar spine BMD were measured using dual energy-X-ray absorptiometry. BMD Z-scores accounted for bone age and sex. Multiple linear regression was used to evaluate differences in Z-scores by HIV status and for predictors of BMD in HIV+. Results: 350 HIV+ and 160 HEU were enrolled. Mean age was 12.6 and 10.7 years for HIV+ and HEU, respectively. Most (87%) HIV+ were receiving HAART. More HIV+ than HEU had total body and lumbar spine Z-scores less than -2.0 (total body: 7 vs. 1%, P = 0.008; lumbar spine: 4 vs. 1%, P = 0.08). Average differences in Z-scores between HIV+ and HEU were attenuated after height and/or weight adjustment. Among HIV+, total body Z-scores were lower in those with higher CD4% and in those who ever used boosted protease inhibitors or lamivudine. Lumbar spine Z-scores were lower with higher peak viral load and CD4%, more years on HAART, and ever use of indinavir. Conclusion: Rates of low BMD in HIV+ children were greater than expected based on normal population distributions. These differences were partially explained by delays in growth. As most HIV+ children in this study had not entered their pubertal growth spurt, prepubertal factors associated with BMD, magnified or carried forward, may result in sub-optimal peak BMD in adulthood.
  • Thumbnail Image
    Item
    CD4 T cells but not Th17 cells are Required for Mouse Lung Transplant Obliterative Bronchiolitis
    (Wiley, 2015-07) Wu, Qiang; Gupta, Pawan Kumar; Suzuki, Hidemi; Wagner, Sarah R.; Zhang, Chen; Cummings, Oscar W.; Fan, Lin; Kaplan, Mark H.; Wilkes, David S.; Shilling, Rebecca A.; Department of Pediatrics, Indiana University School of Medicine
    Lung transplant survival is limited by obliterative bronchiolitis (OB), but the mechanisms of OB development are unknown. Previous studies in a mouse model of orthotopic lung transplantation suggested a requirement for IL-17. We have used this orthotopic mouse model to investigate the source of IL-17A and the requirement for T cells producing IL-17A. The major sources of IL-17A were CD4+ T cells and γδ T cells. Depletion of CD4+ T cells led to a significantly decreased frequency and number of IL-17A+ lymphocytes and was sufficient to prevent acute rejection and OB. However, mice with STAT3-deficient T cells, which are unable to differentiate into Th17 cells, rejected lung allografts and developed OB similar to control mice. The frequency of IL-17A+ cells was not decreased in mice with STAT3-deficient T cells due mainly to the presence of IL-17A+ γδ T cells. Deficiency of γδ T cells also did not affect the development of airway fibrosis. Our data suggest that CD4+ T cells are required for OB development and expansion of IL-17A responses in the lung, while Th17 and γδ T cells are not absolutely required and may compensate for each other.
  • Thumbnail Image
    Item
    CD4+ T cell-mediated neuroprotection is independent of T cell-derived BDNF in a mouse facial nerve axotomy model
    (Elsevier, 2012) Xin, Junping; Mesnard, Nichole A.; Beahrs, Taylor; Wainwright, Derek A.; Serpe, Craig J.; Alexander, Thomas D.; Sanders, Virginia M.; Jones, Kathryn J.; Anatomy, Cell Biology and Physiology, School of Medicine
    Background: The production of neurotrophic factors, such as BDNF, has generally been considered an important mechanism of immune-mediated neuroprotection. However, the ability of T cells to produce BDNF remains controversial. Methods: In the present study, we examined mRNA and protein of BDNF using RT-PCR and western blot, respectively, in purified and reactivated CD4(+) T cells. In addition, to determine the role of BDNF derived from CD4(+) T cells, the BDNF gene was specifically deleted in T cells using the Cre-lox mouse model system. Results: Our results indicate that while both mRNA expression and protein secretion of BDNF in reactivated T cells were detected at 24 h, only protein could be detected at 72 h after reactivation. The results suggest a transient up-regulation of BDNF mRNA in reactivated T cells. Furthermore, in contrast to our hypothesis that the BDNF expression is necessary for CD4(+) T cells to mediate neuroprotection, mice with CD4(+) T cells lacking BDNF expression demonstrated a similar level of facial motoneuron survival compared to their littermates that expressed BDNF, and both levels were comparable to wild-type. The results suggest that the deletion of BDNF did not impair CD4(+) T cell-mediated neuroprotection. Conclusion: Collectively, while CD4(+) T cells are a potential source of BDNF after nerve injury, production of BDNF is not necessary for CD4(+) T cells to mediate their neuroprotective effects.
  • Thumbnail Image
    Item
    Growth and CD4 patterns of adolescents living with perinatally acquired HIV worldwide, a CIPHER cohort collaboration analysis
    (Wiley, 2022) Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) Global Cohort Collaboration; Jesson, Julie; Crichton, Siobhan; Quartagno, Matteo; Yotebieng, Marcel; Abrams, Elaine J.; Chokephaibulkit, Kulkanya; Le Coeur, Sophie; Aké-Assi, Marie-Hélène; Patel, Kunjal; Pinto, Jorge; Paul, Mary; Vreeman, Rachel; Davies, Mary-Ann; Ben-Farhat, Jihane; Van Dyke, Russell; Judd, Ali; Mofenson, Lynne; Vicari, Marissa; Seage, George, III.; Bekker, Linda-Gail; Essajee, Shaffiq; Gibb, Diana; Penazzato, Martina; Collins, Intira Jeannie; Wools-Kaloustian, Kara; Slogrove, Amy; Powis, Kate; Williams, Paige; Matshaba, Mogomotsi; Thahane, Lineo; Nyasulu, Phoebe; Lukhele, Bhekumusa; Mwita, Lumumba; Kekitiinwa-Rukyalekere, Adeodata; Wanless, Sebastian; Goetghebuer, Tessa; Thorne, Claire; Warszawski, Josiane; Galli, Luisa; van Rossum, Annemarie M.C.; Giaquinto, Carlo; Marczynska, Magdalena; Marques, Laura; Prata, Filipa; Ene, Luminita; Okhonskaya, Lyuba; Navarro, Marisa; Frick, Antoinette; Naver, Lars; Kahlert, Christian; Volokha, Alla; Chappell, Elizabeth; Pape, Jean William; Rouzier, Vanessa; Marcelin, Adias; Succi, Regina; Sohn, Annette H.; Kariminia, Azar; Edmonds, Andrew; Lelo, Patricia; Lyamuya, Rita; Ogalo, Edith Apondi; Odhiambo, Francesca Akoth; Haas, Andreas D.; Bolton, Carolyn; Muhairwe, Josephine; Tweya, Hannock; Sylla, Mariam; D'Almeida, Marceline; Renner, Lorna; Abzug, Mark J.; Oleske, James; Purswani, Murli; Teasdale, Chloe; Nuwagaba-Biribonwoha, Harriet; Goodall, Ruth; Leroy, Valériane; Medicine, School of Medicine
    Introduction: Adolescents living with HIV are subject to multiple co-morbidities, including growth retardation and immunodeficiency. We describe growth and CD4 evolution during adolescence using data from the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) global project. Methods: Data were collected between 1994 and 2015 from 11 CIPHER networks worldwide. Adolescents with perinatally acquired HIV infection (APH) who initiated antiretroviral therapy (ART) before age 10 years, with at least one height or CD4 count measurement while aged 10-17 years, were included. Growth was measured using height-for-age Z-scores (HAZ, stunting if <-2 SD, WHO growth charts). Linear mixed-effects models were used to study the evolution of each outcome between ages 10 and 17. For growth, sex-specific models with fractional polynomials were used to model non-linear relationships for age at ART initiation, HAZ at age 10 and time, defined as current age from 10 to 17 years of age. Results: A total of 20,939 and 19,557 APH were included for the growth and CD4 analyses, respectively. Half were females, two-thirds lived in East and Southern Africa, and median age at ART initiation ranged from <3 years in North America and Europe to >7 years in sub-Saharan African regions. At age 10, stunting ranged from 6% in North America and Europe to 39% in the Asia-Pacific; 19% overall had CD4 counts <500 cells/mm3 . Across adolescence, higher HAZ was observed in females and among those in high-income countries. APH with stunting at age 10 and those with late ART initiation (after age 5) had the largest HAZ gains during adolescence, but these gains were insufficient to catch-up with non-stunted, early ART-treated adolescents. From age 10 to 16 years, mean CD4 counts declined from 768 to 607 cells/mm3 . This decline was observed across all regions, in males and females. Conclusions: Growth patterns during adolescence differed substantially by sex and region, while CD4 patterns were similar, with an observed CD4 decline that needs further investigation. Early diagnosis and timely initiation of treatment in early childhood to prevent growth retardation and immunodeficiency are critical to improving APH growth and CD4 outcomes by the time they reach adulthood.
  • Thumbnail Image
    Item
    Pubertal Onset in HIV-infected Children in the Era of Combination Antiretroviral Treatment
    (Wolters Kluwer, 2013) Williams, Paige L.; Abzug, Mark J.; Jacobson, Denise L.; Wang, Jiajia; Van Dyke, Russell B.; Hazra, Rohan; Patel, Kunjal; Dimeglio, Linda A.; McFarland, Elizabeth J.; Silio, Margarita; Borkowsky, William; Seage, George R.; Oleske, James M.; Geffner, Mitchell E.; International Maternal Pediatric and Adolescent AIDS Clinical Trials P219219C Study; Pediatric HIVAIDS Cohort Study; Pediatrics, School of Medicine
    Objective: To evaluate associations of perinatal HIV infection, HIV disease severity, and combination antiretroviral treatment with age at pubertal onset. Design: Analysis of data from two US longitudinal cohort studies (IMPAACT 219C and PHACS AMP), conducted during 2000-2012, including perinatally HIV-infected (PHIV) and HIV-exposed but uninfected (HEU) youth. Tanner stage assessments of pubertal status (breast and pubic hair in girls; genitalia and pubic hair in boys) were conducted annually. Methods: We compared the timing of pubertal onset (Tanner stage ≥2) between PHIV and HEU youth using interval-censored models. For PHIV youth, we evaluated associations of HIV disease severity and combination antiretroviral treatment with age at pubertal onset, adjusting for race/ethnicity and birth cohort. Results: The mean age at pubertal onset was significantly later for the 2086 PHIV youth compared to the 453 HEU children (10.3 vs. 9.6, 10.5 vs. 10.0, 11.3 vs. 10.4, and 11.5 vs. 10.7 years according to female breast, female pubic hair, male genitalia, and male pubic hair staging, respectively, all P < 0.001). PHIV youth with HIV-1 RNA viral load above 10, 000 copies/ml (vs. ≤10, 000 copies/ml) or CD4% below 15% (vs. ≥15%) had significantly later pubertal onset (by 4-13 months). Each additional year of combination antiretroviral treatment was associated with a 0.6-1.2-month earlier mean age at pubertal onset, but this trend did not persist after adjustment for birth cohort. Conclusion: Pubertal onset occurs significantly later in PHIV than in HEU youth, especially among those with more severe HIV disease. However, in the current era, combination antiretroviral treatment may result in more normal timing of pubertal onset.