https://repository.seku.ac.ke/handle/123456789/1817 Mon, 27 Jul 2026 05:31:32 GMT 2026-07-27T05:31:32Z https://repository.seku.ac.ke/handle/123456789/8408 Variances in antiviral memory T-cell repertoire of CD45RA- and CD62L-depleted lymphocyte products reflect the need of individual T-cell selection strategies to reduce the risk of GvHD while preserving antiviral immunity in adoptive T-cell therapy Mangare, Caroline; Tischer-Zimmermann, Sabine; Bonifacius, Agnes; Riese, Sebastian B.; Dragon, Anna C.; Blasczyk, Rainer; Maecker-Kolhoff, Britta; Eiz-Vesper, Britta Introduction: Viral infections and reactivations still remain a cause of morbidity and mortality after hematopoietic stem cell transplantation due to immunodeficiency and immunosuppression. Transfer of unmanipulated donor-derived lymphocytes (DLI) represents a promising strategy for improving cellular immunity but carries the risk of graft versus host disease (GvHD). Depleting alloreactive naïve T cells (TN) from DLIs was implemented to reduce the risk of GvHD induction while preserving antiviral memory T-cell activity. Here, we compared two TN depletion strategies via CD45RA and CD62L expression and investigated the presence of antiviral memory T cells against human adenovirus (AdV) and Epstein-Barr virus (EBV) in the depleted fractions in relation to their functional and immunophenotypic characteristics. Methods: T-cell responses against ppEBV_EBNA1, ppEBV_Consensus and ppAdV_Hexon within TN-depleted (CD45RA−/CD62L−) and TN-enriched (CD45RA+/CD62L+) fractions were quantified by interferon-gamma (IFN-γ) ELISpot assay after short- and long-term in vitro stimulation. T-cell frequencies and immunophenotypic composition were assessed in all fractions by flow cytometry. Moreover, alloimmune T-cell responses were evaluated by mixed lymphocyte reaction. Results: According to differences in the phenotype composition, antigen-specific T-cell responses in CD45RA− fraction were up to 2 times higher than those in the CD62L− fraction, with the highest increase (up to 4-fold) observed after 7 days for ppEBV_EBNA1-specific T cells. The CD4+ effector memory T cells (TEM) were mainly responsible for EBV_EBNA1- and AdV_Hexon-specific T-cell responses, whereas the main functionally active T cells against ppEBV_Consensus were CD8+ central memory T cells (TCM) and TEM. Moreover, comparison of both depletion strategies indicated that alloreactivity in CD45RA− was lower than that in CD62L− fraction. Conclusion: Taken together, our results indicate that CD45RA depletion is a more suitable strategy for generating TN-depleted products consisting of memory T cells against ppEBV_EBNA1 and ppAdV_Hexon than CD62L in terms of depletion effectiveness, T-cell functionality and alloreactivity. To maximally exploit the beneficial effects mediated by antiviral memory T cells in TN-depleted products, depletion methods should be selected individually according to phenotype composition and CD4/CD8 antigen restriction. TN-depleted DLIs may improve the clinical outcome in terms of infections, GvHD, and disease relapse if selection of pathogen-specific donor T cells is not available. https://doi.org/10.1159/000516284 Tue, 01 Feb 2022 00:00:00 GMT https://repository.seku.ac.ke/handle/123456789/8408 2022-02-01T00:00:00Z https://repository.seku.ac.ke/handle/123456789/8407 Robust identification of suitable T-cell subsets for personalized CMV-specific T-cell immunotherapy using CD45RA and CD62L microbeads Mangare, Caroline; Tischer-Zimmermann, Sabine; Riese, Sebastian B.; Dragon, Anna C.; Prinz, Immo; Blasczyk, Rainer; Maecker-Kolhoff, Britta; Eiz-Vesper, Britta Viral infections and reactivations remain a serious obstacle to successful hematopoietic stem cell transplantation (HSCT). When antiviral drug treatment fails, adoptive virus-specific T-cell transfer provides an effective alternative. Assuming that naive T cells (TN) are mainly responsible for GvHD, methods were developed to generate naive T-cell-depleted products while preserving immune memory against viral infections. We compared two major strategies to deplete potentially alloreactive T cells: CD45RA and CD62L depletion and analyzed phenotype and functionality of the resulting CD45RA−/CD62L− naive T-cell-depleted as well as CD45RA+/CD62L+ naive T-cell-enriched fractions in the CMV pp65 and IE1 antigen model. CD45RA depletion resulted in loss of terminally differentiated effector memory T cells re-expressing CD45RA (TEMRA), and CD62L depletion in loss of central memory T cells (TCM). Based on these differences in target cell-dependent and target cell-independent assays, antigen-specific T-cell responses in CD62L-depleted fraction were consistently 3–5 fold higher than those in CD45RA-depleted fraction. Interestingly, we also observed high donor variability in the CD45RA-depleted fraction, resulting in a substantial loss of immune memory. Accordingly, we identified donors with expected response (DER) and unexpected response (DUR). Taken together, our results showed that a naive T-cell depletion method should be chosen individually, based on the immunophenotypic composition of the T-cell populations present. doi:10.3390/ijms20061415 Wed, 20 Mar 2019 00:00:00 GMT https://repository.seku.ac.ke/handle/123456789/8407 2019-03-20T00:00:00Z https://repository.seku.ac.ke/handle/123456789/8406 Red cell allo- and autoimmunisation in transfused sickle cell and cancer patients in Kenyatta National Hospital, Nairobi, Kenya Mangare, Caroline; Mbugua, Amos; Maturi, Peter; Rajab, Jamila; Blasczyk, Rainer; Heuft, Hans-Gert Background: Currently, no data are available on the prevalence of red blood cell (RBC) antibody formation amongst Kenyan patients with multiple transfusion needs, such as patients with sickle cell disease (SCD) or haematological malignancies (HM) and solid (SM) malignancies. Objectives: We determined the prevalence and specificities of RBC alloantibodies and autoantibodies in two patient groups with recurrent transfusion demands at Kenyatta National Hospital, Nairobi, Kenya. Method: Between February and August 2014, 300 samples from SCD, HM and SM patients were collected and screened for alloantibodies. Samples from 51 healthy blood donors were screened for irregular antibodies and phenotyped. Results: Amongst the 228 patients with viable samples (SCD, n = 137; HM, n = 48; SM, n = 43), the median transfusion frequency was two to three events per group, 38 (16.7%) were RBC immunised and 32 (14.0%) had a positive direct antiglobulin test. We identified specific alloantibodies in six patients (2.6%). Four of these six were SCD patients (2.9%) who had specific RBC alloantibodies (anti-Cw, anti-M, anti-Cob, anti-S); amongst HM patients one had anti-K and one had anti-Lea. RBC autoantibody prevalence was 3.1% (7/228). Amongst the healthy blood donors, the Ror, ccD.ee and R2r, ccD.Ee phenotypes accounted for 82% of the Rhesus phenotypes and all were Kell negative. Conclusion: The numbers of transfusions and the rates of RBC alloantibodies are low and the most important RBC alloantibody-inducing blood group antigens are relatively homogeneously distributed in this population. A general change in the Kenyatta National Hospital pre-transfusion test regimen is thus not necessary. The current transfusion practice should be reconsidered if transfusion frequencies increase in the future. DOI: https://doi.org/10.4102/ajlm.v4i1.297 Fri, 25 Sep 2015 00:00:00 GMT https://repository.seku.ac.ke/handle/123456789/8406 2015-09-25T00:00:00Z https://repository.seku.ac.ke/handle/123456789/8400 Social support received by diabetes mellitus type ii patients attending a county referral hospital in Kenya. Akhonya, Wilson L.; Mutunga-Mwenda, Catherine S.; Washika, Esther M. Purpose: Diabetes Mellitus Type II is a condition where the patients present with increased receptor resistance to adequately or normal amount of insulin production and reduced or inadequate amount of insulin produced. Worldwide the approximated burden of DM Type II is at 366 million people in 2011. The objective of the study is to determine the level of social support received by Diabetes Mellitus Type II patients attending a County Referral Hospital in Kenya. Methodology: This was a descriptive cross-sectional study conducted at a County Referral Hospital Outpatient Diabetic Clinic. Researcher administered questionnaires were used to collect data. Data analysis was manual for qualitative data and for quantitative data, descriptive statistics were used to analyze aided by the statistical package for social scientists (SPSS) version 22. Results: Majority 67.91% of the total participants reported not to be socially supported by their family and peers in specific aspects of their self-care management of Diabetes Mellitus Type II that contributed to the sub-optimal self-care practices attributed to the participants. Unique contribution to theory, practice and policy: Study found close relationship between adequate Diabetes Mellitus Type II self-care by DM Type II patients and social support. The researcher recommends in-cooperation of the patient’s social circles in Diabetes Mellitus Type II self-care patients’ education so as to promote understanding which will enhance social support hence optimal practice and adherence. Sat, 01 Jan 2022 00:00:00 GMT https://repository.seku.ac.ke/handle/123456789/8400 2022-01-01T00:00:00Z