P17. Impaired Phenotype and Function of T Follicular Helper Cells in HIV-1-Infected Children Receiving ART.

Bekele Y1,2, Amu S1, Bobosha K2, Lantto R1, Nilsson A3,4, Endale B2, Gebre M5, Aseffa A2, Rethi B1, Howe R2, Chiodi F1.

Affiliates: 1Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden 2Armauer Hansen Research Institute, P.O. Box 1005, Addis Ababa, Ethiopia 3Department of Woman and Child Health, Karolinska Institutet, Stockholm, Sweden 4Pediatric Infectious Diseases Unit at the Pediatric Emergency Department, Astrid Lindgren’s Children Hospital, Stockholm, Sweden 5All Africa Leprosy, Tuberculosis and Rehabilitation Training (ALERT) hospital Addis Ababa, Ethiopia

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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 (P¼0.02). 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.