Altered T cell responses in children with autism

Abstract

Autism spectrum disorders (ASD) are characterized by impairment in social interactions, communication deficits, and restricted repetitive interests and behaviors. A potential etiologic role for immune dysfunction in ASD has been suggested. Dynamic adaptive cellular immune function was investigated in 66 children with a confirmed diagnosis of ASD and 73 confirmed typically developing (TD) controls 2-5 years-of-age. In vitro stimulation of peripheral blood mononuclear cells with PHA and tetanus was used to compare group-associated cellular responses. The production of GM-CSF, TNFα, and IL-13 were significantly increased whereas IL-12p40 was decreased following PHA stimulation in ASD relative to TD controls. Induced cytokine production was associated with altered behaviors in ASD children such that increased pro-inflammatory or T(H)1 cytokines were associated with greater impairments in core features of ASD as well as aberrant behaviors. In contrast, production of GM-CSF and T(H)2 cytokines were associated with better cognitive and adaptive function. Following stimulation, the frequency of CD3(+), CD4(+) and CD8(+) T cells expressing activation markers CD134 and CD25 but not CD69, HLA-DR or CD137 were significantly reduced in ASD, and suggests an altered activation profile for T cells in ASD. Overall these data indicate significantly altered adaptive cellular immune function in children with ASD that may reflect dysfunctional immune activation, along with evidence that these perturbations may be linked to disturbances in behavior and developmental functioning. Further longitudinal analyzes of cellular immunity profiles would delineate the relationship between immune dysfunction and the progression of behavioral and developmental changes throughout the course of this disorder.

Figure 1

Comparison of cellular responses following PHA stimulation in children with autism spectrum disorders (ASD; n = 37) and age-matched typically developing age-matched controls (TD; n =35). Data are expressed as a stimulation index (S.I.). Horizontal box lines are 25%, 50% (median) and 75% of the distribution with whiskers marking 1.5 times the interquartile range.

Figure 2

Increased cytokine responses after stimulation with PHA in children with autism spectrum disorders (ASD; n = 37) compared with age-matched typically developing age-matched controls (TD; n =35). y-axis represents cytokine levels (pg/ml)). Horizontal box lines are 25%, 50% (median) and 75% of the distribution with whiskers marking 1.5 times the interquartile range.