Thymic Rebound Research Articles

Systemic immunostimulation induces glucocorticoid-mediated thymic involution succeeded by rebound hyperplasia which is impaired in aged recipients.

The thymus is the central organ involved with T-cell development and the production of naïve T cells. During normal aging, the thymus undergoes marked involution, reducing naïve T-cell output and resulting in a predominance of long-lived memory T cells in the periphery. Outside of aging, systemic stress responses that induce corticosteroids (CS), or other insults such as radiation exposure, induce thymocyte apoptosis, resulting in a transient acute thymic involution with subsequent recovery occurring after cessation of the stimulus. Despite the increasing utilization of immunostimulatory regimens in cancer, effects on the thymus and naïve T cell output have not been well characterized. Using both mouse and human systems, the thymic effects of systemic immunostimulatory regimens, such as high dose IL-2 (HD IL-2) with or without agonistic anti-CD40 mAbs and acute primary viral infection, were investigated. These regimens produced a marked acute thymic involution in mice, which correlated with elevated serum glucocorticoid levels and a diminishment of naïve T cells in the periphery. This effect was transient and followed with a rapid thymic "rebound" effect, in which an even greater quantity of thymocytes was observed compared to controls. Similar results were observed in humans, as patients receiving HD IL-2 treatment for cancer demonstrated significantly increased cortisol levels, accompanied by decreased peripheral blood naïve T cells and reduced T-cell receptor excision circles (TRECs), a marker indicative of recent thymic emigrants. Mice adrenalectomized prior to receiving immunotherapy or viral infection demonstrated protection from this glucocorticoid-mediated thymic involution, despite experiencing a substantially higher inflammatory cytokine response and increased immunopathology. Investigation into the effects of immunostimulation on middle aged (7-12 months) and advance aged (22-24 months) mice, which had already undergone significant thymic involution and had a diminished naïve T cell population in the periphery at baseline, revealed that even further involution was incurred. Thymic rebound hyperplasia, however, only occurred in young and middle-aged recipients, while advance aged not only lacked this rebound hyperplasia, but were entirely absent of any indication of thymic restoration. This coincided with prolonged deficits in naïve T cell numbers in advanced aged recipients, further skewing the already memory dominant T cell pool. These results demonstrate that, in both mice and humans, systemic immunostimulatory cancer therapies, as well as immune challenges like subacute viral infections, have the potential to induce profound, but transient, glucocorticoid-mediated thymic involution and substantially reduced thymic output, resulting in the reduction of peripheral naive T cells. This can then be followed by a marked rebound effect with naïve T cell restoration, events that were shown not to occur in advanced-aged mice.

FRI042 Worsening Shortness Of Breath After A Mild Case Of Covid-19

Abstract Disclosure: K. Qureshi: None. T.S. Krause: None. K. Vidlock: None. This case demonstrates a complication of COVID 19 that may be more common than we know and overlooked. A 34-year-old female presents to the Emergency Department with worsening shortness of breath and tachycardia for 3 days. Her symptoms are worse with ambulation. She feels dizzy and lightheaded. The patient had COVID-19 about two weeks ago and received monoclonal antibodies. The patient has a history of “drenching” night sweats and unintentional weight loss. She denies fever and cough. The patient is eating and drinking normally with no abdominal pain, nausea, or rash. No changes in bowel movements. The patient’s past medical history consists of ADHD, Anxiety, Neuropathy, and Insomnia. The patient takes Adderall, amitriptyline (ELAVIL), fluocinonide (LIDEX). The patient’s family history consists of an aunt who has autoimmune disease and a maternal grandfather who has Non-Hodgkin's Lymphoma. She works as a medical assistant in a family medicine clinic. Patient underwent a CTA which displayed a new anterior mediastinal mass measuring 4.6 x 2.6 x 3.2 cm which was not shown on a previous CT scan 11 months prior. She was referred to a thoracic surgeon for mediastinoscopy, which couldn’t be performed due to location not adjacent to trachea. A PET scan showed mildly FDG-avid soft tissue density in the anterior mediastinum. Four months later, the patient had a CT scan which showed a modest decrease in size measuring 2.1 x 2.5 cm. The thymus is important in maturation of T cells and is replaced with fat through aging. The thymus plays an important immunological role in defending against pathogens and cancer by maturing and releasing T cells. Thymic hyperplasia is a response that has been displayed in autoimmune diseases such as Myasthenia Gravis. Thymic rebound hyperplasia is seen more often in children, typically after chemotherapy treatment but not seen in adults. Rebound hyperplasia occurs less often with viral illness. There have been a limited number of cases seen with COVID-19. An observational study of 87 participants suggested that rebound thymic hyperplasia may be a positive predictive factor due to the benefit of T-cell lymphocyte production. The presence of thymic hyperplasia on CT scan in COVID patients correlated with a better prognosis in a retrospective study of 325 COVID patients that had a CT scan. This patient will require repeated imaging and follow up. The long-term consequences of this finding are unknown and this patient has a history of night sweats which preceded the COVID course. Presentation: Friday, June 16, 2023

Thymus CT-grading and rebound hyperplasia during COVID-19 infection: a CT volumetric study with multivariate linear regression analysis

BackgroundThe importance of thymic CT-grading and presence of thymic rebound hyperplasia during COVID-19 infection were only investigated in a few studies. This multivariate study aims to evaluate the relation between thymus CT-grading and rebound during COVID-19 infection and the following: (1) the patients' age, (2) the patients' blood lymphocytic count, (3) the CT-volumetry of the diseased lung parenchyma, (4) the patient's clinical course and prognosis, and finally (5) the final radiological diagnosis.ResultsMulticenter retrospective analyses were conducted between March and June 2021 on 325 adult COVID-19 patients with positive PCR results and negative history of malignant or autoimmune diseases. They included 186 males and 139 females (57.2%:42.8%). Their mean age was 40.42 years ± 14.531 SD. Three consulting radiologists performed CT-grading of the thymus gland (grade 0–3) and CT-severity scoring (CT-SS) of the pathological lung changes in consensus. Two consulting pulmonologists correlated the clinical severity and blood lymphocytic count. Pearson correlation coefficient (r) and linear regression analyses were statistically utilized. Sub-involuted thymus (with CT-grade 0:2) was detected in 42/325 patients (12.9%); all of them had a mild clinical course and low CT-SS (0–1). Thymic rebound hyperplasia was the only positive CT-finding in 15/325 patients (4.6%) without pathological lung changes. A weak positive significant correlation was proved between thymic grade and patient's age, clinical course, and CT-SS (r = 0.217, 0.163, and 0.352 with p ≤ 0.0001, < 0.0001, and 0.002, respectively). A weak negative significant correlation was found between thymic grade and lymphocytic count (r = − 0.343 and p ≤ 0.0001). A strong positive significant correlation was encountered between clinical severity against patients' age and CT-SS (r = 0.616 and 0.803 with p ≤ 0.0001).ConclusionsThe presence of sub-involuted thymus or thymic rebound should not be radiologically overlooked in COVID-19 patients. During COVID-19 infection, the presence of sub-involuted thymus with low CT-grading (0–2) was correlated with young age groups, low CT-severity scoring, mild clinical course, and better prognosis (good prognostic factor). It was seldom seen in old hospitalized patients. Atypically, it was also correlated with normal lymphocytic count or even lymphocytosis. The thymic rebound could be the only positive CT-finding even during the absence of lung involvement.

Thymic rebound hyperplasia post-chemotherapy mistaken as disease progression in a patient with lymphoma involving mediastinum: a case report and reflection

BackgroundChemotherapy can cause thymic atrophy and reduce T-cell output in cancer patients. However, the thymus in young adult patients has regenerative potential after chemotherapy, manifesting as thymic hyperplasia which can be easily mistaken as residual disease or recurrence in patients suffering lymphoma.Case presentationThis study reports a case of lymphoma in a young female adult who was initially diagnosed with an anterior mediastinal mass, and was found to have soft tissue occupying the anterior mediastinum repeatedly after chemotherapy, suggesting a lymphoma residue or disease progression. From discussions by a multi-disciplinary team (MDT), the anterior mediastinal mass of the patient was considered unknown and might be thymus tissue or tumor tissue, and it was eventually identified as thymus tissue via histopathology.ConclusionsThe anterior mediastinal mass appearing after chemotherapy in patients with lymphoma can be considered as enlarged thymus, and such phenomenon is frequent in young adult patients who undergo chemotherapy or autologous hematopoietic stem cell transplantation. Additionally, detection of thymic output cells in peripheral blood might be a feasible approach to differentiate thymic hyperplasia from lymphoma.

The role of radiological imaging for masses in the prevascular mediastinum in clinical practice.

Tumors in the prevascular compartment of the mediastinum are rare and imaging plays a major role in their detection, (differential) diagnosis, staging, and follow-up. The prevascular compartment is bordered anteriorly by the posterior aspect of the sternum, posteriorly by the ventral aspect of the pericardium, cranially by the thoracic outlet, and caudally by the diaphragm. In many cases, the diagnosis of a lesion in the prevascular compartment is an incidental finding either on chest radiograph (CR) or on computed tomography (CT) scans. The differential diagnosis of masses in the pre-vascular mediastinum include primarily tumors arising from the thymus or the thyroid gland, lymphomas and germ cell tumors. The differential diagnosis of mediastinal masses is primarily based on the location of the mass, its tissue composition (i.e., fat content, calcifications) and the age of the patient. The imaging method of choice is CT, as it combines a high spatial and temporal resolution with the ability to determine tissue composition and detect fluid components, as well as areas of fat and calcifications. MRI is used as a more specific problem-solving tool to discriminate solid lesions from cystic lesions or to provide evidence of minimal fat content in teratoma and thymic rebound. The role of PET/CT in the evaluation of tumors other than lymphomas in the prevascular compartment is still under discussion.

Intrathymic Deletion of IL-7 Reveals a Contribution of the Bone Marrow to Thymic Rebound Induced by Androgen Blockade.

Despite the well-documented effect of castration in thymic regeneration, the singular contribution of the bone marrow (BM) versus the thymus to this process remains unclear. The chief role of IL-7 in pre- and intrathymic stages of T lymphopoiesis led us to investigate the impact of disrupting this cytokine during thymic rebound induced by androgen blockade. We found that castration promoted thymopoiesis in young and aged wild-type mice. In contrast, only young germline IL-7-deficient (Il7-/- ) mice consistently augmented thymopoiesis after castration. The increase in T cell production was accompanied by the expansion of the sparse medullary thymic epithelial cell and the peripheral T cell compartment in young Il7-/- mice. In contrast to young Il7-/- and wild-type mice, the poor thymic response of aged Il7-/- mice after castration was associated with a defect in the expansion of BM hematopoietic progenitors. These findings suggest that BM-derived T cell precursors contribute to thymic rebound driven by androgen blockade. To assess the role of IL-7 within the thymus, we generated mice with conditional deletion of IL-7 (Il7 conditional knockout [cKO]) in thymic epithelial cells. As expected, Il7cKO mice presented a profound defect in T cell development while maintaining an intact BM hematopoietic compartment across life. Unlike Il7-/- mice, castration promoted the expansion of BM precursors and enhanced thymic activity in Il7cKO mice independently of age. Our findings suggest that the mobilization of BM precursors acts as a prime catalyst of castration-driven thymopoiesis.

Immune rebound associates with a favorable clinical response to autologous HSCT in systemic sclerosis patients

AbstractTo evaluate the immunological mechanisms associated with clinical outcomes after autologous hematopoietic stem cell transplantation (AHSCT), focusing on regulatory T- (Treg) and B- (Breg) cell immune reconstitution, 31 systemic sclerosis (SSc) patients underwent simultaneous clinical and immunological evaluations over 36-month posttransplantation follow-up. Patients were retrospectively grouped into responders (n = 25) and nonresponders (n = 6), according to clinical response after AHSCT. Thymic function and B-cell neogenesis were respectively assessed by quantification of DNA excision circles generated during T- and B-cell receptor rearrangements. At the 1-year post-AHSCT evaluation of the total set of transplanted SSc patients, thymic rebound led to renewal of the immune system, with higher T-cell receptor (TCR) diversity, positive correlation between recent thymic emigrant and Treg counts, and higher expression of CTLA-4 and GITR on Tregs, when compared with pretransplant levels. In parallel, increased bone marrow output of newly generated naive B-cells, starting at 6 months after AHSCT, renovated the B-cell populations in peripheral blood. At 6 and 12 months after AHSCT, Bregs increased and produced higher interleukin-10 levels than before transplant. When the nonresponder patients were evaluated separately, Treg and Breg counts did not increase after AHSCT, and high TCR repertoire overlap between pre- and posttransplant periods indicated maintenance of underlying disease mechanisms. These data suggest that clinical improvement of SSc patients is related to increased counts of newly generated Tregs and Bregs after AHSCT as a result of coordinated thymic and bone marrow rebound.

A Rare Case of Thymic Rebound Hyperplasia

SESSION TITLE: Disorders of the Mediastinum 2 SESSION TYPE: Affiliate Case Report Poster PRESENTED ON: Tuesday, October 31, 2017 at 01:30 PM - 02:30 PM INTRODUCTION: Thymic enlargement, while a rare phenomenon in adults, may occur, mainly after chemotherapy. We present here, to our knowledge, the first case in literature of thymic rebound hyperplasia in an elderly woman with rheumatoid arthritis (RA) CASE PRESENTATION: A 60 year old woman with past medical history of rheumatoid arthritis presented to our chest clinic with complaints of chest pain and dyspnea on exertion. Detailed history revealed patient has a long standing h/o rheumatoid arthritis and has been on various immune suppressants including steroids, methotrexate and tofacitinib but currently taking only NSAIDS for the past 2 months prior to clinic visit. Examination revealed the chest pain mostly of costochondritic nature likely related to her arthritis and she had RA related changes in her fingers and joints. A pulmonary function test revealed restrictive pattern and decreased lung volumes with decreased diffusion capacity, findings likely related to her RA. A CT chest was also obtained to evaluate for connective disease associated ILD which showed an anterior mediastinal mass with morphological and radiological features suggestive of thymic hyperplasia. Patient was closely followed up and subsequent CT’s showed decreasing size of the thymus while the patient remained off chemotherapy for her RA. DISCUSSION: Thymic rebound hyperplasia is a rare but known phenomenon observed more commonly at a younger age. It is usually observed following chemotherapy for various malignancies. One study also reported this phenomenon following radiotherapy for thyroid malignancy. It commonly occurs in children and young adults and more common among females. The thymus appears to atrophy during the administration of chemotherapy and regrow during the recovery phase of chemotherapy. It is a benign immunological rebound phenomenon and does not require operative intervention. This case is unique since it is the first reported case of thymic rebound hyperplasia following immune suppressants in an elderly patient with RA. CONCLUSIONS: Thymic enlargement, while a rare phenomenon in adults, may occur, mainly after chemotherapy. This phenomenon should be included in the differential diagnosis of a soft tissue mass appearing in the anterior mediastinum on CT in adult patients particularly following treatment for malignancy or following chemotherapy for any cause. Reference #1: Rebound thymic enlargement on CT in adults.Yarom N1, Zissin R.Int J Clin Pract. 2007 Apr;61(4):562-8. Epub 2007 Jan 29. DISCLOSURE: The following authors have nothing to disclose: Prarthna Chandar, Sakthidev Kulandaisamy, Mangalore Amith Shenoy, Shyam Shankar, Pavan Irukulla, Benhoor Shamian, Yizhak Kupfer, Kabu Chawla, Michael Bergman No Product/Research Disclosure Information

Autoimmunity and allergy control in adults submitted to complete thymectomy early in infancy.

The contribution of the decline in thymic activity for the emergence of autoimmunity is still debatable. Immune-competent adults submitted to complete thymectomy early in life provide a unique model to address this question. We applied here strict criteria to identify adults lacking thymic activity based on sjTREC levels, to exclude thymic rebound and/or ectopic thymuses. In agreement, they featured severe naïve CD4 T-cell depletion and contraction of T-cell receptor diversity. Notwithstanding this, there was neither increased incidence of autoimmune disease in comparison with age-matched controls nor significant changes in their IgG/IgA/IgM/IgE autoreactivity profiles, as assessed through extensive arrays. We reasoned that the observed relative preservation of the regulatory T-cell compartment, including maintenance of naïve regulatory CD4 T-cells, may contribute to limit the emergence of autoimmunity upon thymectomy. Our findings have implications in other clinical settings with impaired thymic activity, and are particularly relevant to studies of autoimmunity in ageing.

Rebound Thymic Hyperplasia after Chemotherapy in Children with Lymphoma

Development of mediastinal masses after completion of chemotherapy in pediatric patients with malignant lymphoma is worrisome and challenging to clinicians. We performed a retrospective review of 67 patients with lymphoma treated at our hospital from January 1, 2001 to June 1, 2013. Patients who received at least two chest computed tomography (CT) examinations after complete remission (CR) was achieved were further analyzed. Gallium-67 scans and positron emission tomography (PET) were recorded and compared between these patients. Sixty-two of 67 patients reached CR, of whom 31 (22 male, 9 female) were patients that received at least two chest CT examinations after CR. Rebound thymic hyperplasia (RTH) was diagnosed in 21/31 patients (67.7%), including 14/23 (60.9%) and seven out of eight (87.5%) with non-Hodgkin's lymphoma and Hodgkin's lymphoma, respectively. Ages ranged from 3years to 18years (median 10years). Increased radioactivity uptake of the anterior mediastinum in gallium scans was found in nine out of 20 patients (45%) with thymic rebound. PET was performed in six out of 21 patients. Increased fluorodeoxyglucose (FDG)-avid uptake in the anterior mediastinum was observed in four of six patients (66.7%) by PET. One patient received thymectomy. No patients with RTH had lymphoma relapse within the median follow-up period (5years). Relapse was statistically significantly different (p=0.001) between patients with and without RTH. RTH developed in 67.7% of pediatric patients with lymphoma in CR after chemotherapy. The association of RTH development and lowered relapse rates has yet to be determined. Awareness of this phenomenon is important in the prevention of unnecessary surgical intervention or chemotherapy.

Role of T cells in ovariectomy induced bone loss—revisited

Role of T cells in ovariectomy induced bone loss—revisited

Differentiation of Normal Thymus from Anterior Mediastinal Lymphoma and Lymphoma Recurrence at Pediatric PET/CT

To evaluate the role of positron emission tomography (PET)/computed tomography (CT) in the differentiation of normal thymus from mediastinal lymphoma and lymphoma recurrence in pediatric patients. The study was approved by the institutional review board, and informed consent was waived. The study was HIPAA compliant. Two hundred eighty-two fluorine 18 fluorodeoxyglucose PET/CT studies in 75 pediatric oncology patients were reviewed retrospectively. Patients were divided into four groups: anterior mediastinal lymphoma (group A, n=16), anterior mediastinal lymphoma with subsequent recurrence (group B, n=5), lymphoma outside the mediastinum (group C, n=16), and other malignant tumors outside the thymus (group D, n=38). Analyses included measurements of the maximum anteroposterior and transverse dimensions of the anterior mediastinal mass or thymus on axial CT images and measurements of maximum standardized uptake values of anterior mediastinal mass, thymus (SUVt), and bone marrow at the level of the fifth lumbar vertebra (SUVb) on PET images. Quantitative parameters were compared by using an analysis of variance test. Mean prechemotherapy SUVt was 4.82 for group A, 8.45 for group B, 2.00 for group C, and 2.09 for group D. Mean postchemotherapy SUVt for group B was 4.74. Thymic rebound (mean SUVt, 2.89) was seen in 44% of patients at a mean interval of 10 months from the end of chemotherapy. The differences between prechemotherapy SUVt of mediastinal lymphoma and normal thymus and postchemotherapy SUVt of lymphoma recurrence and thymic rebound were highly significant (P<.001). SUVt is a sensitive predictor for differentiation of normal thymus or thymic rebound from mediastinal lymphoma. SUVt of 3.4 or higher is a strong predictor of mediastinal lymphoma.

Thymic Uptake of 18F-FDG Following Radioiodine Ablation Therapy

We report the case of a 47-year-old woman with a history of non-Hodgkin's lymphoma. During the course of her disease, we performed various 18F-FDG PET/CT that identified several significant incidental findings. First, we incidentally identified a hypermetabolic nodule in the left thyroid lobe, whose final diagnosis showed differentiated thyroid carcinoma. Second, metabolic activity was visualized in the thymus secondary to ablative treatment with radioiodine. This uptake disappeared in subsequent studies. Several papers have reported thymic rebound following chemotherapy but we have found only one case report of 18F-FDG uptake after radioiodine treatment. On the other hand, this case is of interest because it supports the benefit of studying the hypermetabolic thyroid nodules incidentally detected on the PET/CT performed for other reasons.

Captación de 18F-FDG en timo tras terapia ablativa de restos tiroideos con 131I

We report the case of a 47 year-old woman with a history of non-Hodgkin's lymphoma. During the course of her disease, we performed various 18FFDG PET/CT that identified several significant incidental findings. First, we incidentally identified a hypermetabolic nodule in the left thyroid lobe, whose final diagnosis was differentiated thyroid carcinoma. Second, metabolic activity was visualized in the thymus secondary to ablative treatment with radioiodine. This uptake disappeared in subsequent studies. Several papers have reported thymic rebound following chemotherapy but we have found only one case report of 18FFDG uptake after radioiodine treatment. On the other hand, this case is of interest because it supports the benefit of studying the hypermetabolic thyroid nodules incidentally detected on the PET/CT performed for other reasons.

Clinical and Radiologic Review of the Normal and Abnormal Thymus: Pearls and Pitfalls

At imaging, the thymus appears in a variety of shapes and sizes, even in the same individual. It gradually involutes with age and may acutely shrink during periods of bodily stress. During the recovery period, it grows back to its original size or even larger, a phenomenon known as thymic rebound hyperplasia. These anatomic variations and dynamic changes appear to be the main source of confusion with pathologic conditions. In turn, these misinterpretations may lead to prolongation or alteration of the chemotherapy regimen or to unnecessary radiation therapy, biopsy, or thymectomy. Familiarity with the embryology, anatomy, and dynamic physiology of the thymus is essential to avoid unnecessary imaging or invasive procedures. Radiologists play a major role in differentiating normal thymic variants, ectopic thymic tissue, and nonneoplastic thymic conditions such as rebound hyperplasia from neoplastic conditions. Knowledge of the imaging findings of thymic tumors and their mimics may help radiologists arrive at the correct diagnosis.

Comblement de la loge thymique après traitement d’une maladie de Hodgkin : rebond ou rechute ?

We report the case of a 36-year-old women with Hodgkin's disease treated with polychemotherapy and bone marrow autograft. Progressive growth of a thymic mass suggested possible relapse four months after treatment withdrawal. This mass did not exhibit gallium-67 uptake but showed strong affinity for 18-FDG (SUV=6.8). Surgical biopsy ruled out recurrence of Hodgkin's disease of the thymus and led to the diagnosis of thymic rebound. The aspect of the thymic compartment returned to normal spontaneously at one year.

Positive gallium-67 and thallium-201 scans in thymic rebound after chemotherapy for lymphoma

It is a diagnostic problem to distinguish thymic rebound or rebound thymic hyperplasia from thymic malignancy, but it is frequently made more difficult because most patients have had previous malignancies. Recently we evaluated a six-year-old girl with thymic rebound after chemotherapy for lymphoma, by both gallium-67 and thallium-201 scans. On gallium-67 scan, intensive uptake was seen in the anterior mediastinum. CT revealed a triangular-shaped, homogeneous mass in the anterior mediastinum. On early scan of thallium-201 study, slight accumulation was seen in the anterior mediastinum and was enhanced in delayed scans. Considering the clinical state and imaging results, thymic rebound after chemotherapy was the most likely diagnosis, and follow-up observation was done without therapy. During the course, there were no signs of relapse. Some reports have described both positive and negative thallium-201 accumulation in thymic rebound. Although more experience with similar cases is necessary, it is likely that thallium-201 also tends to accumulate in thymic rebound as well as gallium-67.

Cervical thymic rebound after cancer treatment

While newly recognized neck masses in children previously treated for malignancy raise the specter of recurrent disease, recent experience with 2 patients has shown us that enlargement of cervical thymic tissue should be considered in the differential diagnosis, especially early after the completion of chemotherapy or immunotherapy.

Age‐related thymic activity in adults following chemotherapy‐induced lymphopenia

The potential role of the adult thymus in T-cell homeostasis subsequent to lymphopenia remains the subject of debate. We examined whether thymic activity contributes to reconstitution of the peripheral T-cell pool, a critical process for patients recovering from antineoplastic therapy. In selected patients with various neoplastic diseases we assessed peripheral blood lymphocyte subsets by flow-cytometry, including thymus-derived, CD4+ T cells expressing the CD45RA molecule, and thymic size rebound by CT scan before, and 3, 6 and 12 months after completion of cytotoxic therapy. Adult patients (n = 21, mean age of 30 years, range 18-49) had higher baseline numbers of B and lower numbers of NK cells than elderly patients (n = 15, mean age of 79 years, range 70-91), while total T-cell numbers did not differ. Despite the reduction of lymphocyte counts being comparable in the adult (mean of 45%) and elderly (mean of 49%) groups, occurring at, or near, completion of treatment, an enlargement of the previously atrophic thymus was evident in 63% of the adult, but in none of the elderly, subjects. In 22 patients who remained active disease-free during the following year, B cells and NK cells recovered to pretreatment levels as soon as at 3 months, whereas overall T-cell recovery occurred at 6 months post-treatment. Thymic rebound, observed in 11 of 22 patients who were of younger age, correlated significantly with a faster and more complete recovery of CD45RA+ CD4+ (mainly helper-naïve) T cells. The adult thymus appears capable of regeneration, at least up to middle age, contributing significantly to the reconstitution of the peripheral T-cell pool following chemotherapy-induced lymphopenia. In advanced age, however, although peripheral homeostatic pathways appear intact, regeneration of the naïve repertoire is incomplete.

Endogenous IL-7 is associated with increased thymic volume in adult HIV-infected patients under highly active antiretroviral therapy.

Immune reconstitution after highly active antiretroviral therapy (HAART) in HIV-infected patients has led to an increase in the number of new CD4 T lymphocytes. Neolymphopoiesis in the thymus has been proposed as a mechanism in T-cell regeneration. Nevertheless, factors involved in the regeneration of T cells by thymic-dependent pathways in HIV-infected patients under HAART are still unknown and might be of relevance in HIV infection. The aim of this work was to study the role of IL-7 in the thymic rebound of HIV-infected adults under HAART. To study the association between IL-7 and thymic function-related markers, these variables were measured in 49 antiretroviral-naive HIV-infected patients at baseline and at weeks 12, 24, 36 and 48 of treatment. Thymic function-related markers: thymic volume, naive phenotype, and T-cell receptor excision circles (TREC) bearing-cells, were evaluated by computed tomography, flow cytometry, and quantitative polymerase chain reaction, respectively. IL-7 levels were evaluated using a high sensitivity colorimetric enzyme-linked immunosorbent assay. At baseline, we found an inverse correlation between IL-7 levels and thymic function-associated parameters: thymic volume, naive T cells and TREC-bearing cells. After 48 weeks of therapy increased levels of thymic function-related markers along with a significant decrease in IL-7 levels were found. IL-7 levels at baseline were the only independently associated variable with respect to changes in thymic volume at weeks 12, 24 and 48 of follow-up. These data suggest that IL-7 plays an important role in thymic rebound in adult HIV-infected patients under HAART.