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T-cell responses to posttranslationally modified self-antigens are associated with many autoimmune disorders. In type 1 diabetes, hybrid insulin peptides (HIPs) are implicated in the T-cell–mediated destruction of insulin-producing β-cells within pancreatic islets. The natural history of the disease is such that it allows for the study of T-cell reactivity prior to the onset of clinical symptoms. We hypothesized that CD4 T-cell responses to posttranslationally modified islet peptides precedes diabetes onset. In a cohort of genetically at-risk individuals, we measured longitudinal T-cell responses to native insulin and hybrid insulin peptides. Both proinflammatory (interferon-γ) and antiinflammatory (interluekin-10) cytokine responses to HIPs were more robust than those to native peptides, and the ratio of such responses oscillated between pro- and antiinflammatory over time. However, individuals who developed islet autoantibodies or progressed to clinical type 1 diabetes had predominantly inflammatory T-cell responses to HIPs. Additionally, several HIP T-cell responses correlated to worsening measurements of blood glucose, highlighting the relevance of T-cell responses to posttranslationally modified peptides prior to autoimmune disease development.

Certain HLA class II genes increase the risk for type 1 diabetes (T1D) development while others provide protection from disease development. HLA class II alleles encode MHC proteins on antigen-presenting cells, which function to present peptides and activate CD4 T cells. The DRB1*15:01 (DR15)-DQA1*01:02-DQB1*06:02 (DQ6) haplotype provides dominant protection across all stages of T1D and is a common haplotype found in Caucasians. However, it is present in

Introduction Highly seasonal animals demonstrate predictable changes in immune function that coincide with changes in photoperiod. Little is known about the effect of season on immune response in baboons. The objective of this study was to determine the effect of season on inflammatory response in baboons. Materials and Methods Peripheral blood mononuclear cell cytokine response following immune stimulation and serum markers of inflammation were assessed during each season in two groups of young male baboons: one housed under natural light and one in a controlled environment of 12 hours light:12 hours dark. Results A seasonal immune rhythm was evident in both groups, with a greater TNF-α and IL-6 response to stimulation and serum CRP concentration in June and September compared with December. Conclusions Season is an important experimental confounder, and therefore, time of year should be controlled when designing studies and analyzing data from immune studies in baboons.

Baboons are an ideal model for studies of human inflammatory response due to their physiological and immunological similarities to people; however; little is known about how age affects immune function in the baboon. We sought to determine if baboons show age-related innate immune changes similar to that described in people. Age was correlated with increased serum C-reactive protein and interleukin-6 or, however, no change in interleukin-10 concentration was observed (n = 120 baboons). Cytokine release from unstimulated peripheral blood mononuclear cells as well as following immune (lipopolysaccharide) stimulation increased with age. When whole blood was assayed, both lipopolysaccharide stimulated and unstimulated samples showed an age-related increase in interleukin-6 response, although the unstimulated cytokine response was reduced compared with that observed in peripheral blood mononuclear cells. Tumor necrosis factor-α response was not related to age. Cytokine response in lipopolysaccharide-stimulated whole blood was negatively correlated with serum DHEA-S concentration and positively correlated with TGF-β concentration.