Immunologic status and sensitivity of peripheral blood T cells to neurotransmitters in patients with optic neuritis

Abstract

Background: Optic neuritis (ON) is an optic nerve inflammation that can result in impairment of visual function. Studying expression patterns of immune cell subpopulations and genes is of importance for revealing the role and influence of each of them in the early ongoing ON pathological process. Purpose: To examine the immunologic status and sensitivity of peripheral blood T cells to adrenaline and acetylcholine neurotransmitters in patients with ON and its sequelae. Material and Methods: The study cohort included 45 patients with idiopathic ON who underwent an examination: group 1, 27 patients with primary acute ON; group 2, 9 patients with partial optic atrophy (POA) following ON; and group 3, 9 patients with loss of posterior pole structure following ON. Group 4 (controls) was composed of 27 healthy volunteers. The specific reactivity of lymphocytes to adrenaline and acetylcholine was assessed using our complex methodology (in conjunction with a parallel sampling method) for assessing the individual’s sensitivity to medicaments (biological regulators) which has been developed at Immunology laboratory, Filatov Institute of Eye Diseases and Tissue Therapy. The methodology involves obtaining lymphocytes from an individual, culturing lymphocytes with examined drugs immunohistochemically, and use of a peroxidase anti-peroxidase method with monoclonal antibodies Results: Patients with acute idiopathic ON showed increased cell immunity activity, with increased absolute numbers of CD3, CD4, and CD8 cells compared to the control group. The CD4:CD8 ratio for acute ON was not significantly different from the norm. We noted increased levels of activity of humoral immunity components (increased absolute numbers of B lymphocytes and increased IgA and IgM levels) in acute ON compared to the control group. A reduction in and normalization of absolute numbers of СD3 and СD4 T cells compared to acute ON were characteristic features of cell-mediated immunity in patients with POA following ON and those with loss of posterior pole structure following ON. The percentage of CD8 cells in patients with POA following ON was lower than in controls. It is these characteristic proportions of immunocompetent cell ratios that mirrored in increased CD4:CD8 ratios in ON groups, which is associated with a reduced level of cytotoxic T cells. Patients in groups 1, 2 and 3 had increased absolute numbers of peripheral blood T cells sensitive to adrenaline, being 3.4-fold, 2.4-fold, and 1.7-fold more than controls, respectively. In addition, patients in groups 1 and 2 had increased absolute numbers of peripheral blood T cells sensitive to acetylcholine, being 2.8-fold and 2.6-fold more than controls, respectively. We found significant direct correlations of the level of the T cells sensitive to adrenaline and acetylcholine with the leukocyte cell count and CD3, CD8, CD19 and CD16 lymphocyte subset counts in patients with ON and its sequelae. Conclusion: The levels of some cell-mediated immunity components (CD3, CD4, and CD8) and humoral immunity components (B lymphocytes, IgA and IgM) were increased in acute ON group compared to controls. The laterality of ON exerted an impact only on the relative number of lymphocytes, proportion of CD8 and CD4:CD8 ratio in total patients. Patients had increased absolute numbers of peripheral blood T cells sensitive to adrenaline and acetylcholine compared to controls. There were significant direct correlations of the level of the T cells sensitive to adrenaline and acetylcholine with the leukocyte cell count and CD3, CD8, CD19 and CD16 lymphocyte subset counts in patients with ON and its sequelae.