Background Lung transplantation (LT) is a highly dynamic segment of solid organ transplantation in which gender plays a central role . Our objective was to investigate the causes of outcome differences between women and men all along the LT pathway. Methods We used data from the COhort in Lung Transplantation (COLT) study (12 participating LT centers). Analyses were performed in three phases: baseline clinical characteristics, peri-transplantation period, and post-transplantation follow-up. Results Overall, 1710 participants (802 women and 908 men) were included in this study. Women were less likely than men to undergo transplantation (91.6% versus 95.6%, p=0.001) and waited longer before transplantation (115 versus 73 days, p<0.001). Female gender and pre-transplant class I anti-HLA antibodies were identified as independent factors associated with longer waiting time duration. Female LT recipients commonly received lungs from height- and sex-matched donors, despite higher female waiting-list mortality and a higher proportion of male donors. Importantly, women with oversized lung transplantation (defined by predicted TLC ratio and weight mismatch) did not have worse survival. The overall post-transplant survival of female recipients was significantly higher than that of male recipients (65.6% versus 57.3%, p<0.001), although the prevalence of specific major LT outcomes did not differ according to gender. Conclusion Women waited longer and were less likely to undergo transplant. Women transplanted with an oversized lung did not have worse survival after transplantation, suggesting that size matching criteria based on pTLC ratio and weight mismatch may be less stringent in this context.
Most kidney transplant recipients who discontinue immunosuppression reject their graft. Nevertheless, a small number do not, suggesting that allogeneic tolerance state (referred to operational tolerance) is achievable in humans. So far, however, the rarity of such patients has limited their study. Because operational tolerance could be linked to anergy, ignorance or to an active regulatory mechanism, we analyzed the blood T-cell repertoire usage of these patients. We report on comparison of T-cell selection in drug-free operationally tolerant kidney recipients (or with minimal immunosuppression), recipients with stable graft function, chronic rejection and healthy individuals. The blood T cells of operationally tolerant patients display two major characteristics: an unexpected strongly altered T-cell receptor (TCR) Vβ usage and high TCR transcript accumulation in selected T cells. The cytokine transcriptional patterns of sorted T cells with altered TCR usage show no accumulation of cytokine transcripts (IL10, IL2, IL13, IFN-γ), suggesting a state of hyporesponsiveness in these patients. Identification of such a potential surrogate pattern of operational toler-ance in transplant recipients under life-long immuno-suppression may provide a new basis and rationale for exploration of tolerance state. However, these data ob-tained in a limited number of patients require further confirmation on larger series. Most kidney transplant recipients who discontinue immunosuppression reject their graft. Nevertheless, a small number do not, suggesting that allogeneic tolerance state (referred to operational tolerance) is achievable in humans. So far, however, the rarity of such patients has limited their study. Because operational tolerance could be linked to anergy, ignorance or to an active regulatory mechanism, we analyzed the blood T-cell repertoire usage of these patients. We report on comparison of T-cell selection in drug-free operationally tolerant kidney recipients (or with minimal immunosuppression), recipients with stable graft function, chronic rejection and healthy individuals. The blood T cells of operationally tolerant patients display two major characteristics: an unexpected strongly altered T-cell receptor (TCR) Vβ usage and high TCR transcript accumulation in selected T cells. The cytokine transcriptional patterns of sorted T cells with altered TCR usage show no accumulation of cytokine transcripts (IL10, IL2, IL13, IFN-γ), suggesting a state of hyporesponsiveness in these patients. Identification of such a potential surrogate pattern of operational toler-ance in transplant recipients under life-long immuno-suppression may provide a new basis and rationale for exploration of tolerance state. However, these data ob-tained in a limited number of patients require further confirmation on larger series.
Allergic asthma is a chronic, inflammatory, respiratory disease caused by an abnormal reactivity against allergens.
Currently, treatments are based on specific immunotherapies, but may have potential deleterious side effects. Among new modalities of immunotherapy currently in development, DNA vaccination presents a promising approach. DNA vaccination enables specific immunotherapy in association with reduced allergenicity.
The aim of this study was to investigate the immunological mechanisms involved in Dermatophagoides farinae 1 (Der f1) DNA vaccination in our murine model of allergic asthma due to house dust mites.
For this purpose, mice have been vaccinated in a prophylactic mode with intramuscular administration of a Der f1-encoding plasmid formulated with the block copolymer 704. Then, allergic asthma was induced by sensitization and intra-nasal provocations with total extract of mite.
Our data show that vaccination with Der f1 DNA does not improve respiratory function in our model of asthmatic mice.
Pulmonary and broncho-alveolar infiltrate were more important in Der f1 vaccinated mice with a specific Th1 immune response caracterized by 1) lymphocytes recruitment, 2) increased IFN γ secretion and 3) an increased IgG2a rate.
However, vaccination with Der f1 also induces a Th2 immune response, marked by an increased of IL-4, IL-5 and IL-13 cytokines.
Der f1 DNA vaccination with 704 vector induces in our asthma model, a specific humoral and cellular response unable to protect mice.
These results could be explained by the vector itself, the amount of DNA administered and the particular immunological context of our model of asthma.
