[Cholecysto-gastric fistulas: case report and literature revision]. / Le fistole colecisto-gastriche. Descrizione di un caso e revisione della letteratura.

Authors report a recent case of cholecysto-gastric fistula. On the basis of their own experience and of the literature, authors discuss the pathogenesis of the cholecysto-enteric fistulas and underline the relative non frequent of fistulas with the stomach. Authors stress the available diagnostic and therapeutic features and believe that this disease deserves, whenever possible, a surgical correction.

Spreading of HIV-specific CD8+ T-cell repertoire in long-term nonprogressors and its role in the control of viral load and disease activity.

Long-term non-progressors (LTNP) represent a minority of human immunodeficiency virus (HIV) infected individuals characterized by stable or even increasing CD4+ T-cell count and by stronger immune responses against HIV than progressors. In this study, HIV-specific effector CD8+ T cells, as detected by both a sensitive ex vivo enzyme-linked immunospot (ELISPOT) assay and specific major histocompatibility complex (MHC) peptide tetramers, were at a low frequency in the peripheral blood of LTNP, and recognized a lower number of HIV peptides than their memory resting cell counterparts. Both factors may account for the lack of complete HIV clearance by LTNP, who could control the viral spread, and displayed a higher magnitude of cytotoxic T lymphocyte (CTL) responses than progressors. By combining cell purification and ELISPOT assays this study demonstrates that both effector and memory resting cells were confined to a CD8+ population with memory CD45RO+ phenotype, with the former being CD28- and the latter CD28+. Longitudinal studies highlighted a relatively stable HIV-specific effector repertoire, viremia, and CD4+ T-cell counts, which were all correlated with maintenance of nonprogressor status. In conclusion, the analysis of HIV-specific cellular responses in these individuals may help define clear correlates of protective immunity in HIV infection.

Virus-specific CD8(+) T cells with type 1 or type 2 cytokine profile are related to different disease activity in chronic hepatitis C virus infection.

The present study demonstrates that the quality of the virus-specific CD8(+) T cell responses, as detected by both enzyme-linked immunospot assay and specific MHC-peptide tetramers, changed in relation to the different disease activity in chronically hepatitis C virus-infected patients. Indeed, both the serum alanine transaminase and the hepatic flogosis levels were related directly to the frequencies of peripheral memory effector CD8(+) T cells producing IFN-gamma (Tc1), but inversely to the frequencies of those producing both IL-4 and IL-10 (Tc2). Longitudinal studies highlighted that Tc1 or Tc2 responses fluctuate in relation to the different phases of the disease in the same individual. Furthermore, the Tc1 or Tc2 phenotype correlates with tetramer-positive cells expressing either CXCR3 or CCR3, promoting differential tissue localization of these cells and the maintenance of T cell homeostasis. Finally, studies at the level of liver-infiltrating lymphocytes indicated that they produced both IFN-gamma and IL-4 with an evident bias towards the Tc1-like phenotype. Our studies suggest that the progressive fluctuation of Tc1 and Tc2 responses may play a fundamental role in maintaining a long-lasting low-level liver inflammation, and may constitute the basis for new therapeutic strategies of immune regulation.

Short-lived immunization site inflammation in self-limited active experimental allergic encephalomyelitis.

To understand the mechanisms underlying spontaneous remission of proteolipid protein (PLP) 139-151 peptide-induced experimental allergic encephalomyelitis (EAE), an acute autoimmune disease of SJL mice resembling human multiple sclerosis, we examined both the effector response site in the central nervous system (CNS) and the immunization site at different phases of the disease. In the CNS, the frequency of PLP 139-151 peptide-specific IFN-gamma-producing T cells as well as the amount of infiltrating CD4(+) and CD11b(+) cells decreased with recovery. However, IL-4-producing cells were always rare and cyclooxygenase-2(+) cells were numerous only at disease peak in the CNS, suggesting that T(h)2 cytokines and prostaglandins did not determine remission of EAE. By looking at the s.c. site of PLP 139-151 peptide plus adjuvant injection, we found that, although the inflammatory infiltrate was abundant, CD11b(+) cells started to decrease already during disease acute phase and DEC-205(+) cells were numerous only at early time points. We propose that immunization site inflammation is short-lived in PLP 139-151 peptide-induced EAE, and this leads to a temporary autoreactive T cell stimulation and to a self-limited disease.

Lack of Th2 cytokine increase during spontaneous remission of experimental allergic encephalomyelitis.

The mechanisms underlying spontaneous remission of autoimmune diseases are presently unknown, though regulatory T cells are believed to play a major role in this process. We tested the hypothesis that Th2 and/or other T cell regulatory cytokines cause the spontaneous remission of experimental allergic encephalomyelitis (EAE), a model of Th1-mediated autoimmunity. We analyzed the cytokine profile of lymph node and central nervous system-infiltrating cells in individual SJL mice at different stages of proteolipid protein (PLP) 139-151 peptide-induced EAE. We found that IFN-gamma slowly fades away after clinical recovery, whereas IL-4, IL-10 and transforming growth factor-beta remain low or undetectable. Our peptide-results therefore suggest that regulatory T cells producing anti-inflammatory cytokines are not involved in spontaneous remission of EAE and challenge the view that the Th1/Th2 balance has a key role in EAE regulation.