Evidence of T cell lymphopenia in the colonic mucosa in idiopathic CD4 lymphocytopenia patients (HEM4P.250)

Abstract

Idiopathic CD4 lymphocytopenia (ICL) is a syndrome of unknown etiology characterized by low peripheral CD4 T cell counts and susceptibility to opportunistic infections. One hypothesis for its etiology is trapping of T cells in effector sites. 11 ICL patients and 16 healthy controls (HC) underwent colonic biopsies for CD3, CD4, and CD8 T cell enumeration by flow cytometry (FC) and immunohistochemistry (IHC) in lamia propria (LP). Mucosal IL17+ CD4 T cells were assessed after PMA/ionomycin stimulation. Plasma levels of LPS (for microbial translocation), I-FABP (for gut epithelial integrity), sCD14 (for monocyte activation), D-dimer (for coagulation) and CRP, IL-6 and TNFalpha (for inflammation) were tested in 33 ICL patients and 44 HC. ICL patients had fewer CD3 (2.84-fold, P=0.0080), CD4 (3.04-fold, P=0.013) and CD8 (2.28-fold, P=0.043) T cells in the colonic mucosa compared to HC by FC and fewer CD3 (2.31-fold, P=0.036) and CD4 (3.81-fold, P=0.0003) T cells in LP by IHC. The proportion of IL-17+ CD4 T cells was higher in ICL compared to HC (6.04 vs 3.35%, P=0.013). Levels of sCD14 levels were slightly higher in ICL than in HC (1.42 vs 1.21 µg/ml, P=0.003). Levels of LPS, I-FABP, IL-6, TNFalpha, D-Dimer, and CRP levels were not significantly different between ICL and HC (all P>0.05). These data suggest that colonic mucosal lymphopenia accompanies peripheral T cell lymphopenia in ICL, albeit with preserved gut epithelial integrity and a lack of systemic inflammation.