Immune Responses Elicited in Tertiary Lymphoid Tissues Display Distinctive Features

During chronic inflammation, immune effectors progressively organize themselves into a functional tertiary lymphoid tissue (TLT) within the targeted organ. TLT has been observed in a wide range of chronic inflammatory conditions but its pathophysiological significance remains unknown. We used the rat aortic interposition model in which a TLT has been evidenced in the adventitia of chronically rejected allografts one month after transplantation. The immune responses elicited in adventitial TLT and those taking place in spleen and draining lymph nodes (LN) were compared in terms of antibody production, T cell activation and repertoire perturbations. The anti-MHC humoral response was more intense and more diverse in TLT. This difference was associated with an increased percentage of activated CD4+ T cells and a symmetric reduction of regulatory T cell subsets. Moreover, TCR repertoire perturbations in TLT were not only increased and different from the common pattern observed in spleen and LN but also “stochastic,” since each recipient displayed a specific pattern. We propose that the abnormal activation of CD4+ T cells promotes the development of an exaggerated pathogenic immune humoral response in TLT. Preliminary findings suggest that this phenomenon i) is due to a defective immune regulation in this non-professional inflammatory-induced lymphoid tissue, and ii) also occurs in human chronically rejected grafts

Mobilité des activités et recomposition des territoires en Méditerranée

En étudiant la mobilité des activités, ce numéro de la revue Méditerranée s’inscrit dans une réflexion sur l’une des transformations majeures de ces trente dernières années : l’essor considérable de l’internationalisation des entreprises, sous l’effet de la libéralisation des mouvements de capitaux et de l’ouverture des marchés. Ayant favorisé un redéploiement significatif de la géographie des activités, cette dynamique s’incarne, selon le lieu, dans les phénomènes de délocalisations facteurs de crise territoriale – ou dans l’émergence de nouveaux territoires, porteurs de croissance et d’attractivité. Nous abordons la mobilité des activités comme un processus multiforme, en privilégiant trois entrées principales : la mobilité des capitaux et les flux d’investissement ; la mobilité des opérateurs économiques (commerçants, cadres et chefs d’entreprises) ; la mobilité des modèles de développement (complexes touristiques, zones franches, technopôles ou pôles de compétitivité…). Ces transformations sont notables en Méditerranée qui, depuis le processus de Barcelone, se trouve au cœur d’un projet de zone de libre‑échange, elles sont aussi marquées par les soubresauts de la crise actuelle et du « printemps arabe ». Mais au-delà du contexte, ne font-elles pas partie des dynamiques de plus longue durée en Méditerranée ? Ce numéro de la revue Méditerranée se saisit de la question au travers d’un panel pluridisciplinaire de contributions

Revisiting human IL-12Rβ1 deficiency: a survey of 141 patients from 30 countries

Interleukin-12 receptor β1 (IL-12Rβ1) deficiency is the most common form of Mendelian susceptibility to mycobacterial disease (MSMD). We undertook an international survey of 141 patients from 102 kindreds in 30 countries. Among 102 probands, the first infection occurred at a mean age of 2.4 years. In 78 patients, this infection was caused by Bacille Calmette-Guérin (BCG; n = 65), environmental mycobacteria (EM; also known as atypical or nontuberculous mycobacteria) (n = 9) or Mycobacterium tuberculosis (n = 4). Twenty-two of the remaining 24 probands initially presented with nontyphoidal, extraintestinal salmonellosis. Twenty of the 29 genetically affected sibs displayed clinical signs (69%); however 8 remained asymptomatic (27%). Nine nongenotyped sibs with symptoms died. Recurrent BCG infection was diagnosed in 15 cases, recurrent EM in 3 cases, recurrent salmonellosis in 22 patients. Ninety of the 132 symptomatic patients had infections with a single microorganism. Multiple infections were diagnosed in 40 cases, with combined mycobacteriosis and salmonellosis in 36 individuals. BCG disease strongly protected against subsequent EM disease (p = 0.00008). Various other infectious diseases occurred, albeit each rarely, yet candidiasis was reported in 33 of the patients (23%). Ninety-nine patients (70%) survived, with a mean age at last follow-up visit of 12.7 years ± 9.8 years (range, 0.5-46.4 yr). IL-12Rβ1 deficiency is characterized by childhood-onset mycobacteriosis and salmonellosis, rare recurrences of mycobacterial disease, and more frequent recurrence of salmonellosis. The condition has higher clinical penetrance, broader susceptibility to infections, and less favorable outcome than previously thought