Dysfunction of infiltrating cytotoxic CD8+ T cells within the graft promotes murine kidney allotransplant tolerance.

Tolerance of mouse kidney allografts arises in grafts that develop regulatory Tertiary Lymphoid Organs (rTLOs). scRNAseq data and adoptive transfer of alloreactive T cells post-transplant showed that cytotoxic CD8+ T cells are reprogrammed within the accepted graft to an exhausted/regulatory-like phenotype mediated by IFN-γ. Establishment of rTLOs was required since adoptive transfer of alloreactive T cells prior to transplantation results in kidney allograft rejection. Despite intragraft CD8+ cells with a regulatory phenotype, they were not essential for the induction and maintenance of kidney allograft tolerance since renal allotransplantation into CD8 KO recipients resulted in acceptance and not rejection. Analysis of scRNAseq data from allograft kidneys and malignant tumors identified similar regulatory-like cell types within the T cell clusters and trajectory analysis showed that cytotoxic CD8+ T cells are reprogrammed into an exhausted/regulatory-like phenotype intratumorally. Induction of cytotoxic CD8+ T cell dysfunction of infiltrating cells appears to be a beneficial mechanistic pathway that protects the kidney allotransplant from rejection through a process we call "defensive tolerance." This pathway has implications for our understanding of allotransplant tolerance and tumor resistance to host immunity.

Menstrual irregularity and poly cystic ovarian syndrome among adolescent girls--a 2 year follow-up study.

OBJECTIVE: To study the clinical outcome after a gap of 2 years, among adolescent girls with confirmed menstrual irregularity and with or without ultrasound diagnosed polycystic ovaries. METHODS: 136 adolescent girls from a cohort of 301 girls between 15 and 17 years of age with confirmed menstrual irregularity, with or without ultrasound diagnosed polycystic ovaries, were assessed in detail after a gap of 2 years. Present menstrual history and symptoms as well as signs of polycystic ovary syndrome (PCOS) were recorded, apart from ultrasound scanning of abdomen. PCOS was diagnosed using Rotterdam's consensus criteria and a comparative analysis was done among cases with and without PCOS. RESULTS: In the phase-II study done after a gap of 2 years, there was a statistically significant lower percentage of irregularities in menses, acne and enlarged thyroid, but a statistically significant increase in hirsuitism as compared to Phase-I study. Of the 136 cases reported, 36.0% cases were found to have PCOS and 63.9% cases were normal. Comparison of the two groups showed a statistically significant higher percentage difference in prevalence of irregular menses (59.9%), hirsuitism (56.3%), acne (17.8%), obesity (17.3%), polycystic ovaries on ultrasound (47.8%) and clinical hyperandrogenism (56.1%) among those with PCOS as against those without PCOS. CONCLUSIONS: The results of this study support screening for menstrual irregularity, obesity and signs of clinical hyperandrogenism for early diagnosis of PCOS in an effort to improve the reproductive health of adolescent girls.

Predictive factors for polypharmacy among child and adolescent psychiatry inpatients.

BACKGROUND: Aim was to determine the predictive factors for polypharmacy among inpatient children and adolescents with psychiatric disorders. METHODS: Blinded, case-note review of children and adolescents with ICD 10 diagnosis of psychiatric disorders on psychotropic medication was conducted. Data on demography, illness, and treatment was analyzed with univariate and multivariate techniques. RESULTS: Proscribing non-pharmacological interventions (OR = 4.7) and pro re nata medication (OR = 3.3), increased the risk of polypharmacy. Prescribing physical restraint reduced the risk of receiving multiple medications (OR = 0.3). CONCLUSION: Proscribing non-pharmacological interventions, pro re nata medication and physical restraints increased polypharmacy.

The changing role of natural killer cells in solid organ rejection and tolerance.

Natural killer (NK) cells have emerged as a particular focus of interest in transplantation due to their ability to distinguish allogeneic major histocompatibility complex (MHC) antigens and their potent cytolytic effector mechanisms. Once relegated to the field of bone marrow transplantation, NK cells have recently been shown to participate in the immune response against solid organ allo- and xenografts. These new findings suggest that the role of NK cells in solid organ rejection and tolerance needs to be reexamined.