Browsing by Subject "CD4"

Now showing 1 - 3 of 3
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    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.
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    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.
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    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.