title: Impaired Phenotype and Function of T Follicular Helper Cells in HIV-1-Infected Children Receiving ART.
abstract: T follicular helper (Tfh) cells are important components in development of specific humoral immune responses; whether the number and biology of Tfh cells is impaired in HIV-1-infected children is not yet studied.The frequency, phenotype, and function of Tfh cells and B cells were determined in blood of HIV-1-infected children receiving antiretroviral therapy (ART) and age-matched controls. Flow cytometry was used to characterize the frequency of Tfh cells and B cell subsets. Cytokine expression was measured after in vitro activation of Tfh cells.A reduced frequency of memory Tfh cells (P < 0.001) was identified in HIV-1-infected children and, on these cells, a reduced expression of programmed death-1 (PD-1) and inducible T cell costimulator (ICOS) (P < 0.001 and P < 0.01). Upon activation, the capacity of Tfh cells to express IL-4, an important cytokine for B cell function, was impaired in HIV-1-infected children.B cell subpopulations in HIV-1-infected children displayed significant differences from the control group: the frequency of resting memory (RM) B cells was reduced (P < 0.01) whereas the frequency of exhausted memory B cells increased (P < 0.001). Interestingly, the decline of RM cells correlated with the reduction of memory Tfh cells (P = 0.02).Our study shows that function and phenotype of Tfh cells, pivotal cells for establishment of adaptive B cell responses, are impaired during HIV-1 infection in children. A consistent reduction of memory Tfh cells is associated with declined frequencies of RM B cells, creating a novel link between dysfunctional features of these cell types, major players in establishment of humoral immunity.
authors.affiliation: From Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden (YB, SA, RL, BR, FC); Armauer Hansen Research Institute, Addis Ababa, Ethiopia (YB, KB, BE, AA, RH); Department of Woman and Child Health, Karolinska Institutet, Stockholm, Sweden (AN); Pediatric Infectious Diseases Unit at the Pediatric Emergency Department, Astrid Lindgren's Children Hospital, Stockholm, Sweden (AN); and All Africa Leprosy, Tuberculosis and Rehabilitation Training (ALERT) Hospital, Addis Ababa, Ethiopia (MG).
authors.forename: Yonas
authors.initials: Y
authors.lastname: Bekele
authors.forename: Sylvie
authors.initials: S
authors.lastname: Amu
authors.forename: Kidist
authors.initials: K
authors.lastname: Bobosha
authors.forename: Rebecka
authors.initials: R
authors.lastname: Lantto
authors.forename: Anna
authors.initials: A
authors.lastname: Nilsson
authors.forename: Birtukan
authors.initials: B
authors.lastname: Endale
authors.forename: Meseret
authors.initials: M
authors.lastname: Gebre
authors.forename: Abraham
authors.initials: A
authors.lastname: Aseffa
authors.forename: Bence
authors.initials: B
authors.lastname: Rethi
authors.forename: Rawleigh
authors.initials: R
authors.lastname: Howe
authors.forename: Francesca
authors.initials: F
authors.lastname: Chiodi
mesh_terms: D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D060889:Inducible T-Cell Co-Stimulator Protein / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008297:Male; D010641:Phenotype; D061026:Programmed Cell Death 1 Receptor / Q000096:biosynthesis; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism*
chemical_list: D044966:Anti-Retroviral Agents; D016207:Cytokines; C556692:ICOS protein, human; D060889:Inducible T-Cell Co-Stimulator Protein; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor