T-follicular helper (Tfh) cells, a specialized subset of CD4⁺ cells, are the immune mediators connecting cellular and humoral immunity, as they lead B-cell proliferation within germinal centers, and orchestrate their response, including activation, class switching, and production of a diverse array of high-affinity antibodies. Their interactions with B cells is regulated by a wide complex of transcriptional and cytokine-driven pathways. A major contribution of Tfh cells to autoimmune diseases is through their production of cytokines, particularly IL-21, which supports the proliferation and differentiation of autoreactive B cells. Elevated levels of circulating Tfh-like cells and IL-21 have been observed in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) correlating strongly with disease severity and autoantibody levels. The feedback loop between Tfh cells and IL-21 or other signal pathways, such as Bcl-6, ICOS, and PD-1, not only sustains Tfh cell function but also drives the continuous expansion of autoreactive B cells, leading to chronic inflammation through the production of high-affinity pathogenic autoantibodies. By understanding these interactions, Tfh pathways may serve as potential therapeutic targets, with IL-21, ICOS, and PD1 blockades emerging as promising innovative therapeutic strategies to manage autoimmune diseases. Although a variety of studies have been conducted investigating the role of Tfh cells in SLE and RA, this review aims to reveal the gap in the literature regarding the role of such subpopulations in the pathogenesis of other autoimmune diseases, such as Anca-associated vasculitis (AAV), and express the need to conduct similar studies. Tfh cell-related biomarkers can be used to assess disease activity and transform autoimmune disease treatment, leading to more personalized and effective care for patients with chronic autoimmune conditions.

Background: End-stage renal disease (ESRD) is associated with alterations in T-cell immunity, including increased CD28null and reduced regulatory T cells (Tregs). However, whether immune disturbances are due to ESRD or primary disease is not yet clear. As diabetes mellitus is the leading cause of ESRD, we evaluated its impact on the immune profile of ESRD patients. Methods: CD28null, Tregs, and natural killer cells were initially analyzed by flow cytometry in 30 predialysis ESRD patients due to diabetes (DM), 30 non-DM (NDM), and 25 healthy controls. Measurements were repeated after 6 months on hemodialysis (HD) or peritoneal dialysis (CAPD). Results: The percentage of CD4 + CD28null cells, CD8 + CD28null cells, and Tregs showed significant differences in DM, NDM, and controls; mean rank 33.71 vs. 25.68 vs. 18.88, p = 0.006, 37.79 vs. 28.82 vs. 17.08, p = 0.008, and 20.79 vs. 26.12 vs. 41.33, p = 0.001, respectively. DM vs. NDM had increased CD4 + CD28null and CD8 + CD28null cells, 11.5% (1.5%–24%) vs. 4.1% (0–42.3%), p = 0.02 and 61.3% (24%–76%) vs. 43% (5.7%–85%), p = 0.04, respectively. After 6 months on HD but not CAPD, DM showed a significant further increase in CD4 + CD28null cells, from 30 (14–100) to 52.7 (15–203), p = 0.02; and CD8 + CD28null cells, from 137 (56–275) to 266 (103–456), p = 0.01. Conclusions: Diabetes mellitus affects T-cell subtypes even at predialysis stage, though changes become more prominent after commencement on HD.

Lupus nephritis (LN), a chronic inflammatory disease, is characterized by the substantial disruption of immune homeostasis. This study examines its effects on the T lymphocyte phenotype and, particularly, its senescence- and exhaustion-related immune alterations. T cell subpopulations were determined with flow cytometry in 30 LN patients and 20 healthy controls (HCs), according to the expression of senescence- (CD45RA, CCR7, CD31, CD28, CD57), and exhaustion- (PD1) related markers. The immune phenotype was associated with disease activity and renal histology. LN patients were characterized by pronounced lymphopenia, mainly affecting the CD4 compartment, with a concurrent reduction in the naïve, central and effector memory subsets compared to the HCs. In the CD8 compartment, the naïve subsets were significantly lower than that of the HCs, but a shift in the T cells occurred towards the central memory population. CD4+PD1+ and CD8+PD1+ cells were increased in the LN patients compared to the HCs. However, in CD4 T cells, the increase was limited to CD45RA+, whereas in CD8 T cells, both CD45RA+ and CD45RA− subsets were affected. Disease activity was correlated with CD4+PD1+ and highly differentiated CD4+CD28-CD57+ cells. Histology was only associated with CD4 T cell disturbances, with stage IV presenting reduced naïve and increased senescent subsets. Exhausted T lymphocyte subpopulations predominate within LN patients, while the T cell phenotype varies depending on disease activity.

Immunosenescence encompasses a spectrum of lymphocyte phenotypic alterations. The aim of the study was to evaluate immunosenescent effect of two different forms of chronic inflammation, Systemic Lupus Erythematosous (SLE), a systemic autoimmune disease, and End-Stage Kidney Disease (ESKD), a chronic inflammatory disorder. Certain lymphocyte surface molecules, including CD31, CD45RA, CCR7, CD28, CD57, for T, and IgD, CD27 for B lymphocytes, were analyzed by flow cytometry in 30 SLE and 53 ESKD patients on hemodialysis (HD), and results were compared to 31 healthy controls (HC) of similar age, gender, and nationality. Significant Lymphopenia was evident in both SLE and ESKD-HD patients, compared to HC, affecting B cells 75.4 (14.4–520.8), 97 (32–341), and 214 (84–576) cells/μL, respectively, p < 0.0001, and CD4 cells 651.2 (71.1–1478.2), 713 (234–1509), and 986 (344–1591) cells/μL, respectively, p < 0.0001. The allocation of B cell subpopulations was remarkably different between SLE and ESKD-HD patients. SLE showed a clear shift to senescence (CD19IgD-CD27−) cells, compared to ESKD-HD and HC, 11.75 (10)% vs. 8 (6) vs. 8.1 (10), respectively. Regarding T lymphocytes, Central Memory CD8 cells predominated in both SLE and ESKD-HD patients compared to HC, 53 (50)%, 52 (63), and 24 (64)%, respectively, while ESKD-HD but not SLE patients also had increased expression of CD4CD28− and CD8CD28− cells. In conclusion, both diseases are followed by significant lymphopenia; however, the senescent phenomenon affects the B lymphocyte compartment in SLE patients and T lymphocytes in ESKD-HD patients.

B and T lymphocytes demonstrate important alterations in patients with systemic lupus erythematous (SLE), with a significant upregulation of double negative (DN) B cells. The aim of this study was to evaluate the correlation of T cell immunity changes with the distinct B-cell-pattern SLE. In the present study, flow cytometry was performed in 30 patients in remission of SLE and 31 healthy controls to detect DN B cells (CD19+IgD-CD27-) and a wide range of T lymphocyte subpopulations based on the presence of CD45RA, CCR7, CD31, CD28, and CD57, defined as naive, memory, and advanced differentiated/senescent T cells. Both B and T lymphocytes were significantly reduced in SLE patients. However, the percentage of DN B cells were increased compared to HC (12.9 (2.3–74.2) vs. 8 (1.7–35), p = 0.04). The distribution of CD4 and CD8 lymphocytes demonstrated a shift to advanced differentiated subsets. The population of DN B cells had a significant positive correlation with most of the early differentiated T lymphocytes, CD4CD31+, CD4CD45RA+CD28+, CD4CD45RA+CD57-, CD4CD45RA-CD57-, CD4CD28+CD57-, CD4CD28+CD57+, CD4 CM, CD8 CD31+, CD8 NAÏVE, CD8CD45RA-CD57-, CD8CD28+CD57-, and CD8CD28+CD57+. Multiple regression analysis revealed CD4CD31+, CD8CD45RA-CD57-, and CD8CD28+CD57- cells as independent parameters contributing to DN B cells, with adjusted R² = 0.534 and p < 0.0001. The predominance of DN B cells in patients with SLE is closely associated with early differentiated T lymphocyte subsets, indicating a potential causality role of DN B cells in T lymphocyte activation.

Background/Objectives: The purpose of this study was to evaluate numerical changes in immune cells after successful kidney transplantation and associate their recovery with clinical and laboratory factors. Methods: In 112 kidney transplant recipients, we performed flow cytometry to evaluate counts of CD4+, CD8+, and regulatory T cells (Tregs), as well as natural killer (NK) cells, before kidney transplantation (T0) and three (T3), six (T6), and twelve (T12) months later. The results were associated with the recipient’s age, cold ischemia time (CIT), the type of donor, dialysis method and vintage, and graft function in one year. Results: Total and CD8+ T cell counts increased gradually one year post transplantation in comparison with pre-transplantation levels, whereas the number of CD4+ T cells and Tregs increased, and the number of NK cells decreased in the first three months and remained stable thereafter. The recipient’s age was negatively correlated with total, CD4+, and Treg counts at T12, whereas CIT affected only total and CD4+ T cell count. Moreover, recipients receiving kidneys from living donors presented better recovery of all T cell subsets at T12 in comparison with recipients receiving kidneys from cadaveric donors. Patients on peritoneal dialysis had increased numbers of total and CD8+ T cells, as well as NK cells. Finally, estimated glomerular filtration rate was positively correlated with Treg level and potentially CD4+ T cells one-year post transplantation. Conclusions: Successful kidney transplantation results in the recovery of most T cell subsets. Lower recipient age and better graft function contribute to increased T cell counts, whereas donor type and dialysis modality are the most important modifiable factors for optimal immune recovery.