The purpose of this study is to evaluate the effects of neonatal thymectomy in the functional capacity of the immune system. We selected a group of 23 subjects, who had undergone thymectomy in their first 30 days of life, during an intervention for congenital heart disease. Several parameters of the immune system were evaluated during their first 3 years of life. Lymphocyte populations and subpopulations (including naive, memory and effector subpopulations), T cell receptor (TCR) Vβ repertoire, response of T cells following in vitro stimulation by mitogen, quantification of immunoglobulins, TCR excision circles (TRECS) and interleukin (IL)-7 were measured. We found that neonatal thymectomy produces long-term diminution in total lymphocyte counts, especially in naive CD4⁺ and CD8⁺ T cells. Additionally, TRECS were decreased, and plasma IL-7 levels increased. A statistically significant negative correlation was found between absolute CD4⁺ T cells and IL-7 (r = −0·470, P = 0·02). The patients did not suffer more infectious events than healthy control children, but thymectomy in neonates resulted in a significant decrease in T lymphocyte levels and TRECS, consistent with cessation of thymopoiesis. This could produce a compromise in immune function later in life, especially if the patients suffer T cell depletion and need a reconstitution of immune function.

The Th1/Th2 balance plays a crucial role in the progression of different pathologies and is a determining factor in the evolution of infectious diseases. This work has aimed to evaluate the early, or on diagnosis, T-cell compartment response, T-helper subsets and anti-SARS-CoV-2 antibody specificity in COVID-19 patients and to classify them according to evolution based on infection severity. A unicenter, randomized group of 146 COVID-19 patients was divided into four groups in accordance with the most critical events during the course of disease. The immunophenotype and T-helper subsets were analyzed by flow cytometry. Asymptomatic SARS-CoV-2 infected individuals showed a potent and robust Th1 immunity, with a lower Th17 and less activated T-cells at the time of sample acquisition compared not only with symptomatic patients, but also with healthy controls. Conversely, severe COVID-19 patients presented with Th17-skewed immunity, fewer Th1 responses and more activated T-cells. The multivariate analysis of the immunological and inflammatory parameters, together with the comorbidities, showed that the Th1 response was an independent protective factor for the prevention of hospitalization (OR 0.17, 95% CI 0.03–0.81), with an AUC of 0.844. Likewise, the Th1 response was found to be an independent protective factor for severe forms of the disease (OR 0.09, 95% CI: 0.01–0.63, p = 0.015, AUC: 0.873). In conclusion, a predominant Th1 immune response in the acute phase of the SARS-CoV-2 infection could be used as a tool to identify patients who might have a good disease evolution.

We examined intraepithelial lymphocytes (IELs) in 213 ileal biopsies from 16 bowel grafts and compared them with 32 biopsies from native intestines. During the first year posttransplantation, grafts exhibited low levels of IELs (percentage of CD103⁺ cells) principally due to reduced CD3⁺CD8⁺ cells, while CD103⁺CD3^– cell numbers became significantly higher. Changes in IEL subsets did not correlate with histology results, isolated intestine, or multivisceral transplants, but CD3^– IELs were significantly higher in patients receiving corticosteroids. Compared with controls, more CD3^– IELs of the grafts expressed CD56, NKp44, interleukin (IL)‐23 receptor, retinoid‐related orphan receptor gamma t (RORγt), and CCR6. No difference was observed in granzyme B, and CD3^–CD127⁺ cells were more abundant in native intestines. Ex vivo, and after in vitro activation, CD3^– IELs in grafts produced significantly more interferon (IFN)‐γ and IL‐22, and a double IFNγ⁺IL‐22⁺ population was observed. Epithelial cell–depleted grafts IELs were cytotoxic, whereas this was not observed in controls. In conclusion, different from native intestines, a CD3^– IEL subset predominates in grafts, showing features of natural killer cells and intraepithelial ILC1 (CD56⁺, NKp44⁺, CCR6⁺, CD127^–, cytotoxicity, and IFNγ secretion), ILC3 (CD56⁺, NKp44⁺, IL‐23R⁺, CCR6⁺, RORγt⁺, and IL‐22 secretion), and intermediate ILC1–ILC3 phenotypes (IFNγ⁺IL‐22⁺). Viability of intestinal grafts may depend on the balance among proinflammatory and homeostatic roles of ILC subsets.

The present study is an analysis of the frequencies of HLA-A and -B antigens and HLA haplotypes in two groups of individuals homozygous for the two main HFE mutations (C282Y and H63D) and a group heterozygous for the S65C mutation. The study population includes: 1123 healthy individuals, 100 homozygous for the C282Y mutation, 138 homozygous for the H63D mutation and 17 heterozygous for the S65C mutation. HFE and HLA alleles were detected using DNA-based and microlymphocytotoxicity techniques respectively. An expected significant association between C282Y and the HLA-A3/B7 haplotype was found, but other HLA haplotypes carrying the -A3 antigen were found: HLA-A3/B62 and HLA-A3/B44. Also, a significant association between H63D mutation and HLA-A29/B44 haplotype was found, and again other HLA haplotypes carrying the HLA-A29 antigen were also found: HLA-A29/B14 and HLA-A29/B62. In addition, the S65C mutation seems to be associated with a HLA haplotype carrying the HLA-A26 antigen. These findings clearly suggest that HLA-A3/B7 and HLA-A29/B44 are the ancestral haplotypes from which the C282Y and H63D mutations originated, respectively. The frequencies of these mutations in different populations, their geographical distribution, and the degree of the statistical association to the ancestral haplotypes, suggest that the H63D mutation must have occurred earlier than the C282Y mutation.

Background We previously reported that preformed anti-MHC class I–related chain A (MICA) antibodies increase the risk for renal graft rejection and enhance the deleterious effect of PRA⁺ status early after transplantation. Methods We studied 727 kidney recipients. Days to reach optimal serum creatinine level, estimated glomerular filtration rate (eGFR) at Month 3 and chronic kidney disease (CKD) stages were recorded. Anti-MICA specificities and C1q binding were tested by solid-phase assay. Complement-dependent cytotoxicity (CDC) and flow cytometry (FC) cross-matches with HeLa and PMA/CD28-T-blasts were performed. Results PRA⁺MICA⁺ recipients exhibited longer time to reach optimal serum creatinine level after transplantation (P = 0.005) and had the lowest eGFR at Month 3 (P = 0.006). PRA⁺MICA⁺ status independently increased the risk for CKDT stage 5 at Month 3 [hazard ratio (HR) 4.92, P = 0.030]. Pre-transplant anti-MICA antibodies were polyspecific and showed stronger reactions when coexisting with anti-HLA antibodies (mean standard fluorescent intensity 112 157 ± 44 426 in HLA⁺MICA⁺ sera versus 49 680 ± 33 116 in HLA⁻MICA⁺ sera, P = 0.0006). Anti-AYVE supereplet reactivity was significantly higher in HLA⁺MICA⁺ versus HLA⁻MICA⁺ patients (P < 0.001) and significantly superior than anti-CMGWS supereplet within HLA⁺MICA⁺ patients (P = 0.001). Three of 13 anti-MICA⁺ pre-transplant sera were positive for the C1q binding assay; one of them (serum 3) exclusively recognized AYVE supereplet with a strong reactivity against MICA*027 antigen (same as MICA*008). Anti-MICA antibodies in anti-HLA-absorbed serum 3 bound native MICA molecules in MICA*008⁺ HeLa and PMA/CD28-T-blasts and mediated cell death by activating complement. Conclusion Preformed anti-MICA antibodies may occasionally be cytotoxic by fixing and activating complement. This way they might contribute to worse early kidney graft function.