New Research on T cell dysfunction

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Brain Behav Immun. 2010 Sep 9. [Epub ahead of print]

Altered T cell responses in children with autism.

Ashwood P, Krakowiak P, Hertz-Picciotto I, Hansen R, Pessah IN, Water JV.

Department of Medical Microbiology and Immunology, University of California,

, CA; Department of Public Health Sciences, Division of Epidemiology,

University of California, , CA.

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 TH1 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.

PMID: 20833247 [PubMed - as supplied by publisher]