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CD4(+) regulatory T cells play a critical role in tolerance induction in transplantation. CD8(+) suppressor T cells have also been shown to control alloimmune responses in preclinical and clinical models. However, the exact nature of the CD8(+) suppressor T cells, their induction and mechanism of function in allogeneic transplantation remain elusive. In this study, we show that functionally suppressive, alloantigen-specific CD8(+) Foxp3(+) T cells can be induced and significantly expanded by stimulating naïve CD8(+) T cells with donor dendritic cells in the presence of IL-2, TGF-β1 and retinoic acid. These CD8(+) Foxp3(+) T cells express enhanced levels of CTLA-4, CCR4 and CD103, inhibit the up-regulation of costimulatory molecules on dendritic cells, and suppress CD4 and CD8 T cell proliferation and cytokine production in a donor-specific and contact-dependent manner. Importantly, upon adoptive transfer, the induced CD8(+) Foxp3(+) T cells protect full MHC-mismatched skin allografts. In vivo, the CD8(+) Foxp3(+) T cells preferentially traffic to the graft draining lymph node where they induce conventional CD4(+) Foxp3(+) T cells and concurrently suppress effector T cell expansion. We conclude that donor-specific CD8(+) Foxp3(+) suppressor T cells can be induced and exploited as an effective form of cell therapy for graft protection in transplantation., (© Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Dendritic cells (DCs) conditioned with the mammalian target of rapamycin (mTOR) inhibitor rapamycin have been previously shown to expand naturally existing regulatory T cells (nTregs). This work addresses whether rapamycin-conditioned donor DCs could effectively induce CD4(+)CD25(+)Foxp3(+) Tregs (iTregs) in cell cultures with alloantigen specificities, and whether such in vitro-differentiated CD4(+)CD25(+)Foxp3(+) iTregs could effectively control acute rejection in allogeneic islet transplantation. We found that donor BALB/c bone marrow-derived DCs (BMDCs) pharmacologically modified by the mTOR inhibitor rapamycin had significantly enhanced ability to induce CD4(+)CD25(+)Foxp3(+) iTregs of recipient origin (C57BL/6 (B6)) in vitro under Treg driving conditions compared to unmodified BMDCs. These in vitro-induced CD4(+)CD25(+)Foxp3(+) iTregs exerted donor-specific suppression in vitro, and prolonged allogeneic islet graft survival in vivo in RAG(-/-) hosts upon coadoptive transfer with T-effector cells. The CD4(+)CD25(+)Foxp3(+) iTregs expanded and preferentially maintained Foxp3 expression in the graft draining lymph nodes. Finally, the CD4(+)CD25(+)Foxp3(+) iTregs were further able to induce endogenous naïve T cells to convert to CD4(+)CD25(+)Foxp3(+) T cells. We conclude that rapamycin-conditioned donor BMDCs can be exploited for efficient in vitro differentiation of donor antigen-specific CD4(+)CD25(+)Foxp3(+) iTregs. Such in vitro-generated donor-specific CD4(+)CD25(+)Foxp3(+) iTregs are able to effectively control allogeneic islet graft rejection.

This study reports the development of adaptive processes in two groups of adolescents assessed initially and 2 years later with clinical research interviews. Students from a public high school (N = 44) and inpatients on an adolescent psychiatric ward (N = 51) formed the two subject groups. The psychiatrically hospitalized group had significantly improved scores after a 2-year interval on four of six adaptive process Summary Scales: Task Orientation, Relatedness, Self Knowledge, and Inner Synthetic Functions. However, these higher scores did not reach the levels of the high school group at either point of assessment. The scores in the high school group remained stable over time except for an increase in the area of Self Knowledge. The value of this interview-derived assessment, in comparison to other forms of measurement, is discussed, and consideration is given to factors which contribute to the differences between groups.

A patient with idiopathic calcification of the basal ganglia (ICBG) manifested a schizophrenialike psychosis beginning at age 17 and later developed a complex movement disorder and mild dementia. Extensive calcification of the basal ganglia was demonstrated by computerized tomography. Review of reported cases of ICBG suggests that patients who become symptomatic early in adulthood are more likely to present with psychosis, whereas those presenting later in life typically manifest dementia and a motor system disorder. ICBG, like other conditions affecting subcortical structures, can produce schizophrenialike symptoms that may precede the onset of intellectual deterioration and extrapyramidal motor disturbances.

Thirteen patients with dementia of the Alzheimer type (DAT) were tested for their ability to read aloud and to read with comprehension. Reading aloud was preserved in all but the most severely impaired cases and was found to be relatively independent of intellectual deterioration. Reading comprehension declined progressively with increasing dementia severity and correlated well with quantitative mental status assessments. The results suggest that the pattern of reading deterioration may aid in the clinical identification of DAT, that the disturbance of reading comprehension is a linguistic deficit rather than a product of visual-perceptual disturbances, and that the alexia is more consistent with an instrumental loss than a de-developmental model of dementia.

Ego defense mechanisms were studied in three groups of early adolescents: diabetic patients, non-psychotic psychiatric patients, and healthy high school students. Defenses were assessed from ratings of open-ended, in-depth interviews. High levels of denial and low levels of asceticism were found in all three groups. Comparisons between groups indicated that psychiatric patients had a distinctive profile of defense usage, in comparison to adolescents from the other two groups. An independent measure of ego development was positively correlated with the defenses of altruism, intellectualization, and suppression, while it was negatively correlated with acting out, avoidance, denial, displacement, projection, and repression. The findings of substantial differences in defense usage between the psychiatric and non-psychiatric samples, and the size and directions of the correlations with ego development level, lend support to the validity of the defense codes.