Summary:The factors affecting T cell reconstitution post haematopoietic cell transplantation (HCT) are not well characterised. We carried out a longitudinal analysis of T cell reconstitution in 32 HCT recipients during the first 12 months post transplant. We analysed reconstitution of naı¨ve, memory and effector T cells, their diversity and monitored thymic output using TCR rearrangement excision circles (TRECs). Thymic-independent pathways were responsible for the rapid reconstitution of memory and effector T cells less than 6 months post HCT. Thymic-dependent pathways were activated between 6 and 12 months in the majority of patients with naı¨ve T cell numbers increasing in parallel with TREC levels. Increasing patient age, chronic GVHD and T cell depletion (with or without pretransplant Campath-1H) predicted low TREC levels and slow naı¨ve T cell recovery. Furthermore, increasing patient age also predicted high memory and effector T cell numbers. The effects of post HCT immunosuppression, total body irradiation, donor leucocyte infusions, T cell dose and post HCT infections on T cell recovery were also analysed. However, no effects of these single variables across a variety of different age, GVHD and T cell depletion groups were apparent. This study suggests that future analysis of the factors affecting T cell reconstitution and studies aimed at reactivating the thymus through therapeutic intervention should be analysed in age-, GVHD-and TCD-matched patient groups. While each of these parameters may have mutually exclusive effects on the outcome of the transplant, it is the combination of all of these parameters that will determine the ultimate success of the transplant. Furthermore, the effects of each of these parameters on immune reconstitution post HCT are unclear.The immediate post transplant period is followed by a severe and often prolonged immune deficiency that results in prolonged susceptibility to infection. 8,17,[19][20][21][22] Although infections that occur in the first month after engraftment probably result from deficiencies in both granulocytes and other mononuclear cell subsets, the more prolonged immune deficiency arises from deficiencies in effective CD4 þ T cell and B cell reconstitution and immunosuppressive therapy. 23,[27][28][29] It was then suggested that the reconstitution and maintenance of effective T cell immunity after HCT was dependent on education of T cell precursors in the thymus. [30][31][32] Furthermore, these observations generated considerable interest in the factors affecting the reconstitution of T cell immunity through thymic-dependent pathways. 33,34 Using phenotypic markers of T cell naivety (primarily the CD45RA antigen), initial studies demonstrated that increasing patient age had an adverse effect on the regeneration of naı¨ve CD4 þ T cells, presumably due to age-related thymic involution, 31 observations that were confirmed using the TCR rearrangement excision circle (TREC) assay to measure thymic output. 35,36 In addition, the thymus has been demonstrated to be...

Experimental allergic encephalomyelitis (EAE), an animal model for multiple sclerosis (MS), is a paralytic disease of the central nervous system (CNS) mediated by T-lymphocytes reactive to myelin basic protein (MBP). Lewis rats actively immunized with fragment 68 to 82 of guinea pig MBP develop a monophasic disease with spontaneous recovery. Lymphocyte recognition of the primary encephalitogenic sequence of MBP (fragment 68 to 82) is V beta 8.2 T cell receptor (TCR) skewed [1-3]. Lewis rats in clinical remission at 1 month and 3 months after spontaneous resolution of EAE retain V beta 8.2 T-lymphocytes in the CNS when analyzed by reverse transcriptase polymerase chain reaction or in situ hybridization. In contrast, 1 and 3 months after clinical remission from syngeneic bone marrow transplantation, V beta 8.2 T lymphocytes are absent from the CNS. During clinically active EAE and inflammatory breakdown of the blood-brain barrier, immune ablation and reconstitution with syngeneic bone marrow results in clinical tolerance of the new immune system to myelin.

Background. Treatment of advanced uterine cervical cancer has advanced little in the last 15 years. Although two phase III trials showed survival benefit with the addition of consolidation chemotherapy (CT) after cisplatin-based chemoradiotherapy (RTCT), it is not considered standard of care. We aimed to evaluate the benefit of consolidation CT compared to no additional treatment in patients treated with RTCT. Methods. This is a retrospective study including 186 patients with FIGO stage IB2, IIA2, or IIB to IVB (paraaortic lymph nodes only) uterine cervical cancer who were treated with standard RTCT alone or RTCT followed by consolidation CT. Overall survival (OS), progression free survival (PFS), and the risk of distant and local relapses were compared between the two treatment groups. Results. At 3 years OS was 91% versus 82.3% (p=0.027), PFS 84.3% versus 54.4% (p=0.047), and distant metastasis free survival (DMFS) 80.4% versus 62.5% (p=0.027) in favor of the consolidation CT group. Multivariate analysis confirmed the benefit of consolidation CT. There was no difference in locoregional free survival (LRFS). Positive lymph node was related to a higher risk of distant relapse. In the lymph node positive subgroup consolidation CT resulted in longer OS (p=0.050), PFS (p=0.014), and DMFS (p=0.022); in the lymph node negative subgroup there was no benefit from consolidation CT. Conclusions. Use of consolidation CT resulted in longer OS and PFS, mostly due to control of distant relapses. Patients at higher risk of distant relapse showed the greatest benefit. This data generates a hypothesis that could help to better select patients to consolidation CT.

Cervical cancer remains a leading cause of morbidity and mortality amongst females in Latin America (LATAM). Cervical cancer is a preventable disease and HPV vaccination is a main key strategy towards its elimination. This study analyzes HPV vaccine implementation current status and the main barriers to achieve adequate coverage in the region. Data from the nineteen sovereign states of LATAM (comprised of all Portuguese and Spanish-speaking nations located south of the United States) were collected, including year of HPV vaccine implementation, gender and age targets, the number of doses included in the public program and coverage by dose. Sixteen out of the 19 evaluated countries have already implemented HPV vaccination programs. However, despite its proven efficacy and safety, HPV vaccine uptake in LATAM has been lower than expected. There is an evident decline in adhesion, mainly regarding the second dose. Several reasons are probably involved, of note: limited knowledge of HPV and HPV vaccine, misguided safety concerns, high cost, cultural barriers, and the Covid19 pandemic. Proper strategies to overcome these barriers are needed to ensure successful uptake. Effective policies are: adopting the one dose schedule, delivering the vaccine on both health center and schools, and advising health professionals to recommend the vaccine. Further research regarding HPV vaccine hesitancy in Latin America is needed.