Pre-Existing Hypertension Is Related with Disproportions in T-Lymphocytes in Older Age

Age-related immune deficiencies increase the risk of comorbidities and mortality. This study evaluated immunosenescence patterns by flow cytometry of naïve and memory T cell subpopulations and the immune risk profile (IRP), expressed as the CD4/CD8 ratio and IgG CMV related to comorbidities. The disproportions in naïve and memory T cells, as well as in the CD4/CD8 ratio, were analysed in 99 elderly individuals (71.9 ± 5.8 years) diagnosed with hypertension (n = 51) or without hypertension (n = 48), using an eight-parameter flow cytometer. The percentage of CD4+ T lymphocytes was significantly higher in hypertensive than other individuals independently from CMV infections, with approximately 34% having CD4/CD8 > 2.5, and only 4% of the elderly with hypertension having CD4/CD8 < 1. The elderly with a normal BMI demonstrated the CD4/CD8 ratio ≥ 1 or ≤ 2.5, while overweight and obese participants showed a tendency to an inverted CD4/CD8 ratio. CD4/CD8 ratio increased gradually with age and reached the highest values in participants aged >75 years. The decline in CD4+ naïve T lymphocytes was more prominent in IgG CMV+ men when compared to IgG CMV+ women. The changes in naïve and memory T lymphocyte population, CD4/CD8, and CMV seropositivity included in IRP are important markers of health status in the elderly that are dependent on hypertension.

Ramsey Hunt syndrome in the child: case report and treatment approach

Herpes zoster is a manifestation of the reactivation of an infection after chickenpox. One of the manifestations of herpes zoster is Ramsey Hunt syndrome, which develops when the ganglion of the VII pair of cranial nerves is involved in process. Diagnosis of Ramsey Hunt syndrome is often based on a combination of a rash in the outer ear and peripheral paresis of the facial muscles. The article describes a rare clinical case of herpes zoster in a child without clinical signs of immunodeficiency, with the development of unilateral paralysis of the facial muscles, pleocytosis in the cerebrospinal fluid. Therapy was performed with a combination of acyclovir and high doses of methylprednisolone with a good clinical effect. It is first mentioning of deviations in the immune status (decreased concentration of the number of markers of naive T‑lymphocytes (TREC)) were revealed, which could be associated with the development of herpes zoster in a child.

Human immunodeficiency reveals GIMAP5 as lymphocyte-specific regulator of senescence

Elucidating the molecular basis of immunodeficiency diseases is a powerful approach to discovering new immunoregulatory pathways in humans. Here we report 10 affected individuals from 4 families with a new immunodeficiency disease comprising of severe progressive lymphopenia, autoimmunity, immunodeficiency, and liver disease due to recessive loss of function variants in “GTPase of immunity-associated proteins” protein 5 (GIMAP5). We show that the disease involves the progressive loss of naïve T lymphocytes and a corresponding increase in antigen-experienced, but poorly functional and replicatively senescent T cells. In vivo treatment of Gimap5-deficient mice with rapamycin (an inhibitor of mTORC1) significantly restores the fraction of naïve T lymphocytes. Furthermore, a GIMAP5-deficient human patient who was treated with rapamycin (sirolimus) showed a remarkable reduction in spleen/lymph node size. Together, these observations reveal that GIMAP5 plays a critical role in lymphocyte metabolism which is essential for senescence prevention and immune competence, suggesting that an inhibitor of mTORC1 could be a valuable clinical intervention in treating patients deficient for GIMAP5.

Modern strategies and capabilities for activation of the immune response against tumor cells

Dendritic cells are professional antigen-presenting cells and the most potent stimulators of various immune responses, such as antitumor responses. Modern studies have not shown an effective antitumor immune response development in patients with malignant tumors. The major cause is the decrease in functional activity of dendritic cells in cancer patients through irregularities in the maturation process to a functionally active form and in the antigen presentation process to naive T lymphocytes. This review describes the main stages of cellular antitumor immune response induction in vitro, aimed at resolving the problems that are blocking the full functioning of dendritic cells, and additional stimulation of antitumor immune response.

Temporal fate mapping reveals age-linked heterogeneity in naive T lymphocytes in mice

Understanding how our T-cell compartments are maintained requires knowledge of their population dynamics, which are typically quantified over days to weeks using the administration of labels incorporated into the DNA of dividing cells. These studies present snapshots of homeostatic dynamics and have suggested that lymphocyte populations are heterogeneous with respect to rates of division and/or death, although resolving the details of such heterogeneity is problematic. Here we present a method of studying the population dynamics of T cells in mice over timescales of months to years that reveals heterogeneity in rates of division and death with respect to the age of the host at the time of thymic export. We use the transplant conditioning drug busulfan to ablate hematopoetic stem cells in young mice but leave the peripheral lymphocyte compartments intact. Following their reconstitution with congenically labeled (donor) bone marrow, we followed the dilution of peripheral host T cells by donor-derived lymphocytes for a year after treatment. Describing these kinetics with mathematical models, we estimate rates of thymic production, division and death of naive CD4 and CD8 T cells. Population-averaged estimates of mean lifetimes are consistent with earlier studies, but we find the strongest support for a model in which both naive T-cell pools contain kinetically distinct subpopulations of older host-derived cells with self-renewing capacity that are resistant to displacement by naive donor lymphocytes. We speculate that these incumbent cells are conditioned or selected for increased fitness through homeostatic expansion into the lymphopenic neonatal environment.

Collaborating with the Enemy: Function of Macrophages in the Development of Neoplastic Disease

Due to the profile of released mediators (such as cytokines, chemokines, growth factors, etc.), neoplastic cells modulate the activity of immune system, directly affecting its components both locally and peripherally. This is reflected by the limited antineoplastic activity of the immune system (immunosuppressive effect), induction of tolerance to neoplastic antigens, and the promotion of processes associated with the proliferation of neoplastic tissue. Most of these responses are macrophages dependent, since these cells show proangiogenic properties, attenuate the adaptive response (anergization of naïve T lymphocytes, induction of Treg cell formation, polarization of immune response towards Th2, etc.), and support invasion and metastases formation. Tumor-associated macrophages (TAMs), a predominant component of leukocytic infiltrate, “cooperate” with the neoplastic tissue, leading to the intensified proliferation and the immune escape of the latter. This paper characterizes the function of macrophages in the development of neoplastic disease.