T cells are crucial for the control of cytomegalovirus (CMV) in infected individuals. Although CMV-specific T cells can be quantified by various methods, clear correlates of protection from CMV disease have not been defined. However, responses to the pp65 protein are believed to play an important role. Here, the proportions of interferon γ–producing T cells following ex vivo activation with pools of overlapping peptides representing the pp65 and immediate early (IE)-1 proteins were determined at multiple time points and related to the development of CMV disease in 27 heart and lung transplant recipients. Frequencies of IE-1–specific CD8 T cells above 0.2 and 0.4% at day 0 and 2 wk, respectively, or 0.4% at any time during the first months discriminated patients who did not develop CMV disease from patients at risk, 50–60% of whom developed CMV disease. No similar distinction between risk groups was possible based on pp65-specific CD8 or CD4 T cell responses. Remarkably, CMV disease developed exclusively in patients with a dominant pp65-specific CD8 T cell response. In conclusion, high frequencies of IE-1 but not pp65-specific CD8 T cells correlate with protection from CMV disease. These results have important implications for monitoring T cell responses, adoptive cell therapy, and vaccine design.

Multiple sclerosis (MS) is an autoimmune neurodegenerative disease characterized by chronic brain inflammation. Leukocyte infiltration of brain tissue causes inflammation, demyelination and the subsequent formation of sclerotic plaques, which are a hallmark of MS. Activation of proinflammatory cytokines is essential for regulation of lymphocyte migration across the blood brain barrier. We demonstrate increased levels of many cytokines, including IL2Ra, CCL5, CCL11, MIF, CXCL1, CXCL10, IFNγ, SCF and TRAIL, were upregulated in CSF, whereas IL17, CCL2, CCL3, CCL4 and IL12(p40) were activated in MS serum. Interaction analysis of cytokines in CSF demonstrated a connection between IFNγ and CCL5 as well as MIF. Many cells can contribute to production of these cytokines including CD8 and Th1 lymphocytes and astrocytes. Therefore, we suggest that IFNγ released by Th1 lymphocytes can activate astrocytes, which then produce chemoattractants, including CCL5 and MIF. These chemokines promote an inflammatory milieu and interact with multiple chemokines including CCL27 and CXCL1. Of special note, upregulation of CCL27 was found in CSF of MS cases. This observation is the first demonstrate CCL27 as a potential contributor of brain pathology in MS. Our data suggests that CCL27 may be involved in activation and migration of autoreactive encephalitogenic immune effectors in the brain. Further, our data supports the role of Th1 lymphocytes in the pathogenesis of brain inflammation in MS, with several cytokines playing a central role.

Background: Cytokine gene polymorphisms may have an impact on the susceptibility to and progression of chronic periodontitis. In this study, we analyzed the −1082 interleukin‐10 (IL‐10), −308 tumor necrosis factor‐alpha (TNF‐α), transforming growth factor‐beta 1 (TGF‐β1) (codons 10 and 2‐), −174IL‐6, and +874 interferon‐gamma (IFN‐γ) gene single‐nucleotide polymorphisms in a cohort of patients with chronic periodontal disease.Methods: The diagnosis was made on the basis of standardized clinical and radiographic criteria. A total of 122 adult patients with chronic periodontitis and 114 unrelated, ethnically and age‐matched white control subjects were genotyped by a polymerase chain reaction–sequence‐specific primer.Results: The number of individuals carrying the −174IL‐6 CC genotype was significantly higher in the group of patients than in the control group (odds ratio [OR] = 1.896; 95% confidence interval [CI] = 1.106 to 3.250; P = 0.0283). The TGF‐β1 (codon 25) GG (Arg²⁵/Arg²⁵) genotype was detected more frequently in control subjects than in periodontitis patients (OR = 0.459; 95% CI = 0.230 to 0.920; P = 0.0421).Conclusion: The −174IL‐6 and TGF‐β1 (codon 25) single‐nucleotide polymorphisms are associated with susceptibility to chronic periodontitis in the population studied.

HLA-A2 is the most frequent HLA molecule in Caucasians with HLA-A*0201 representing the most frequent allele; it was also the first human HLA allele for which peptide binding prediction was developed. The Bioinformatics and Molecular Analysis Section of the National Institutes of Health (BIMAS) and the University of Tübingen (Syfpeithi) provide the most popular prediction algorithms of peptide/MHC interaction on the World Wide Web. To test these predictions, HLA-A*0201-binding nine-amino acid peptides were searched by both algorithms in 19 structural CMV proteins. According to Syfpeithi, the top 2% of predicted peptides should contain the naturally presented epitopes in 80% of predictions (www.syfpeithi.de). Because of the high number of predicted peptides, the analysis was limited to 10 randomly chosen proteins. The top 2% of peptides predicted by both algorithms were synthesized corresponding to 261 peptides in total. PBMC from 10 HLA-A*0201-positive and CMV-seropositive healthy blood donors were tested by ex vivo stimulation with all 261 peptides using crossover peptide pools. IFN-γ production in T cells measured by CFC was used as readout. However, only one peptide was found to be stimulating in one single donor. As a result of this work, we report a potential new T cell target protein, one previously unknown CD8-T cell-stimulating peptide, and an extensive list of CMV-derived potentially strong HLA-A*0201-binding peptides that are not recognized by T cells of HLA-A*0201-positive CMV-seropositive donors. We conclude that MHC/peptide binding predictions are helpful for locating epitopes in known target proteins but not necessarily for screening epitopes in proteins not known to be T cell targets.