Indirect CD4+ TH1 response, antidonor antibodies and diffuse C4d graft deposits in long-term recipients conditioned by donor antigens priming.

Priming of recipients by DST induces long-term survival of mismatched allografts in adult rats. Despite these recipients developing inducible T regulatory cells able to transfer long-term graft survival to a secondary host, a state of chronic rejection is also observed. We revisited the molecular donor MHC targets of the cellular response in acute rejection and analyzed the cellular and humoral responses in recipients with long-term graft survival following transplantation. We found three immunodominant peptides, all derived from LEW.1W RT1.D(u) molecules to be involved in acute rejection of grafts from unmodified LEW.1A recipients. Although the direct pathway of allorecognition was reduced in DST-treated recipients, the early CD4+ indirect pathway response to dominant peptides was almost unimpaired. We also detected early and sustained antidonor class I and II antibody subtypes with diffuse C4d deposits on graft vessels. Finally, long-term accepted grafts displayed leukocyte infiltration, endarteritis and fibrosis, which evolved toward vascular narrowing at day 100. Altogether, these data suggest that the chronic graft lesions developed in long-term graft recipients are the result of progressive humoral injury associated with a persisting indirect T helper response. These features may represent a useful model for understanding and manipulating chronic active antibody-mediated rejection in human.

Humoral and cellular responses to influenza vaccination in human recipients naturally tolerant to a kidney allograft.

Rare kidney allograft recipients enjoy unaltered graft function years after interruption of their immunosuppressive treatment. To assess the extent to which this state of 'operational tolerance' (TOL) is specific to the graft and not the result of a global immunodeficiency, we analyzed the response of such patients following influenza vaccination. Hemagglutination inhibition titers and frequency of IFNgamma-secreting T cells were measured before 1 and 3 months after vaccination. The proportion of healthy volunteers (HV) responding to vaccine was significantly higher than that of immunosuppressed (IS) patients. Three 'TOL' patients presented a humoral response similar to that of HV, whereas the two others had a poor response, like the IS recipients. Although the small number of patients does not allow for definitive conclusions to be made, these data suggest that the status of tolerance may be heterogeneous, with some patients with a global immunodeficiency and others with an adapted response to vaccination.

[Proprioceptive afferents of the transcortical reflex in motor epilepsy:localisation of their thalamic relay in the cat (author's transl)]. / Afférences proprioceptives du réflexe transcortical dans l'épilepsie motrice: localisation du relais thalamique chez le chat.

In the Cat with a penicillin motor focus, a transcortical reflex (RTC) can be triggered by stimulation of the muscle or the cutaneous branch of the radial nerve (DR - SR). We tried here to identify at a suprabulbar level, the proprioceptive pathway involved in triggering RTC. Cerebellar ablation did not modify the reflex. On the other hand reversibly inactivation of a rostral-dorso-medial part of VPL (VPLr) receiving short latency proprioceptive afferents, reversibly abolished the TRC elicited through DR stimulation, while SR stimulation was still effective. It is thus assumed that muscle and cutaneous afferents responsible for eliciting the RTC run in parallel pathways with distinct relay zones within the VPL nucleus.U