Analysis of the T and B cell compartments in tonsils of children with Trisomy 21

GATTI G; GARAY A; LUCIA BOFFELLI; PACHECO A; JEREMÍAS DUTTO; MONTES C; KHAN A

Congreso; Reunión Anual de Sociedades de Biociencias SAIC-SAI-SAFIS 2020; 2020

Trisomy 21(T21) is the most frequent chromosomal disorder in humans withapproximately 1/700 live births, caused by an inherited extra copy of humanchromosome 21. Children with T21 have a unique disease spectrum withincreased incidence of obstructive sleep apnea, tonsil hypertrophy,susceptibility to autoimmunity, a severe reduction in switched memory B cellsand poor response to vaccination (Farroni et al., 2018; www.ndss.org). Sincefollicular helper T cells (Tfh) facilitate B-cell activation and differentiation, westudied Tfh cells in tonsils obtained from two children with T21 whose tonsilswere extracted due to hypertrophy and two age-matched controls, one of themwith recurrent tonsillitis and the other with hypertrophy. We performedimmunohistochemistry and multiparametric flow cytometry to characterize thedifferent subsets. Our preliminary data indicate that the diameters of follicles inT21 tonsils were reduced compared to controls (~500 vs 700 µm). Thefrequencies of CD19+ and CD3+ cells among the total tonsil CD45+ cellpopulation were not modified in T21 samples. The frequency of the CD3 + PD1 highpopulation, associated with germinal center Tfh, was reduced compared to agematched controls (27% vs 36%). Also, the frequency of CD3 + PD1 int wasincreased in T21 tonsils (38% vs 28%). The expression of the activation markerCD38, measured as mean fluorescence intensity (MFI), is reduced in bothCD3+ population (MFI-CD38 PD1int = 2066 vs 3037; MFI-CD38 PD1hi = 5393 vs 8454).We also analyzed the frequencies of the different B cell populations determinedby the expression of CD19, CD27, CD24 and CD38 markers and we observedan increase in the CD19 + CD38 high CD24 high cell population, associated with atransitional phenotype (3,1% vs 1,6%). Our results open new avenues to keepon investigating the B and Tfh response in children with Down Syndrome.