scholarly journals Cyclophosphamide effect on paracoccidioidomycosis in the rat

1995 ◽  
Vol 37 (3) ◽  
pp. 219-224 ◽  
Author(s):  
J. L. Blejer ◽  
C. M. Godio ◽  
R Negroni ◽  
M. R. Nejamkis

Paracoccidioidomycosis is an endemic fungal disease widely distributed throughout Latin America. The potent immunosuppressor cyclophosphamide (CY) has been used to modulate host immune response to Paracoccidioides brasiliensis in an experimental model. Inbred male Buffalo/Sim rats weighing 250-300 g were inoculated with 5 x 10(6) P. brasiliensis cells of the yeast phase form by intracardiac route. One group of animals was treated with 20 mg/kg body weight at days +4, +5, +6, +7, +11 and +12 post-infection (pi.), while a control group was infected alone. No mortality was recorded in either group. Treated rats presented: a) a decrease in granuloma size, which contained less fungal cells; b) a lack of specific antibodies up to 35 days pi., and c) a significant increase in the footpad swelling test (DTH) against paracoccidioidin. Splenic cell transfer from CY-treated P. brasiliensis-infected donors to recipients infected alone led to a significant increase in DTH response in the latter versus untreated infected controls. Likewise, in treated infected recipients transferred with untreated infected donor spleen cells, footpad swelling proved greater than in controls. Thus, it would seem that each successive suppressor T lymphocyte subset belonging to the respective cascade may be sensitive to repeated CY doses administered up to 12 days pi.. Alternatively, such CY schedule may induce the appearance of a T cell population capable of amplifying DTH response.

1982 ◽  
Vol 101 (3) ◽  
pp. 354-358 ◽  
Author(s):  
Bengt Hallengren ◽  
Arne Forsgren

Abstract. To explore suppressor T lymphocyte function in Graves' disease, studies were performed in one group of patients in the hyperthyroid state and in another group in the euthyroid state after treatment. Peripheral blood lymphocytes were cultured for 1–7 days., Pokeweed mitogen (PWM; 1.25 μg/ml) was added at the initiation of the cultures or after 24 h. The degree of lymphocyte activation was assessed by measurements of the cellular uptake of [3H]thymidine and expressed in counts per minute (cpm). The suppressor lymphocyte function was estimated by a quotient between the maximum cpm values from cultures with and without pre-incubation. For the hyperthyroid group (n = 15) the quotient was 1.00 ± 0.07 (mean ± sem), for the euthyroid patient group (n = 21) 1.12 ± 0.05 and for the healthy control group (n = 21) 1.37 ± 0.08. There was a significant difference between the quotients for the control group and the hyperthyroid (P < 0.01) as well as the euthyroid (P < 0.05) patient group. The quotients for the two groups of patients did not differ significantly. In conclusion, the present study supports the view of a defect in suppressor T lymphocyte function in patients with Graves' disease in the hyperthyroid state and indicates that this defect can persist in the euthyroid state after treatment.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Marco Iannetta ◽  
Francesco Buccisano ◽  
Daniela Fraboni ◽  
Vincenzo Malagnino ◽  
Laura Campogiani ◽  
...  

AbstractThe aim of this study was to evaluate the role of baseline lymphocyte subset counts in predicting the outcome and severity of COVID-19 patients. Hospitalized patients confirmed to be infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) were included and classified according to in-hospital mortality (survivors/nonsurvivors) and the maximal oxygen support/ventilation supply required (nonsevere/severe). Demographics, clinical and laboratory data, and peripheral blood lymphocyte subsets were retrospectively analyzed. Overall, 160 patients were retrospectively included in the study. T-lymphocyte subset (total CD3+, CD3+ CD4+, CD3+ CD8+, CD3+ CD4+ CD8+ double positive [DP] and CD3+ CD4− CD8− double negative [DN]) absolute counts were decreased in nonsurvivors and in patients with severe disease compared to survivors and nonsevere patients (p < 0.001). Multivariable logistic regression analysis showed that absolute counts of CD3+ T-lymphocytes < 524 cells/µl, CD3+ CD4+ < 369 cells/µl, and the number of T-lymphocyte subsets below the cutoff (T-lymphocyte subset index [TLSI]) were independent predictors of in-hospital mortality. Baseline T-lymphocyte subset counts and TLSI were also predictive of disease severity (CD3+  < 733 cells/µl; CD3+ CD4+ < 426 cells/µl; CD3+ CD8+ < 262 cells/µl; CD3+ DP < 4.5 cells/µl; CD3+ DN < 18.5 cells/µl). The evaluation of peripheral T-lymphocyte absolute counts in the early stages of COVID-19 might represent a useful tool for identifying patients at increased risk of unfavorable outcomes.


2021 ◽  
pp. jim-2021-001788
Author(s):  
Xiumei Liu ◽  
Xueming Wang ◽  
Xiaoling Zhang ◽  
Ai hua Cao

Tic disorders (TD) are childhood-onset neurological disorders. Immune system dysregulation has been postulated to play a role in TD, and its mechanisms likely involve dysfunctional neural-immune cross-talk, which ultimately leads to altered maturation of the brain pathways that control different TD clinical manifestations and behavioral and emotional damages. Clinical studies have demonstrated an association between TD and allergies and overactive immune responses at a systemic level. In this study, the Yale Global Tic Severity Scale was taken as a global measure of tic severity. Compared with the control group, the group of children with TD plus allergic diseases displayed significantly increased Yale total scores (p<0.05), which suggests that children with TD plus allergic diseases have heavier tic symptoms. Both motor and vocal tic scores are higher in the group of children with TD plus allergy compared with the control group. We counted immune cell subpopulations using FACS. T lymphocyte subset comparison of CD3, CD4, CD8, and CD4:CD8 expression ratios revealed that the level of CD3, CD4, and CD4:CD8 in children with TD plus allergic diseases was significantly lower than those of children with TD without allergic diseases. These differences were statistically significant (p<0.05) and suggest that children with TD plus allergic diseases have imbalanced T lymphocyte subsets. We concluded that allergy increased the severity of TD through an imbalance in cellular immunity. Studies need to be done to show whether treatment of allergic symptoms leads to a decrease in TD manifestations.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yan-Long Ren ◽  
Tao-Tao Li ◽  
Wei Cui ◽  
Li-Min Zhao ◽  
Na Gao ◽  
...  

AbstractInterferon-gamma (IFN-γ) is a cytokine involved in the pathogenesis of Takayasu’s arteritis (TAK). However, the source of IFN-γ in TAK patients is not fully clear. We aimed to investigate the source of IFN-γ in TAK. 60 TAK patients and 35 health controls were enrolled. The lymphocyte subsets of peripheral blood were detected by flow cytometry, cytokines were detected by Bio-plex. The correlation among lymphocyte subsets, cytokines and disease activity indexes was analyzed by person correlation. The level of serum IFN-γ in TAK patients was significantly increased (P < 0.05). The percentage of CD3+IFN-γ+ cells in peripheral blood CD3+ cells was significantly higher in TAK patients than that of healthy control group (P = 0.002). A higher proportion of CD3+CD8+IFN-γ+ cells/CD3+IFN-γ+ cells (40.23 ± 11.98% vs 35.12 ± 11.51%, P = 0.049), and a significantly lower CD3+CD4+IFN-γ+/ CD3+CD8+IFN-γ+ ratio (1.34 ± 0.62% vs 1.80 ± 1.33%, P = 0.027) were showed in the TAK group than that of control group. The CD3+CD8+IFN-γ+/CD3+IFN-γ+ ratio was positively correlated with CD3+IFN-γ+cells/ CD3+cells ratio (r = 0.430, P = 0.001), serum IFN-γ level (r = 0.318, P = 0.040) and IL-17 level (r = 0.326, P = 0.031). It was negatively correlated with CD3+CD4+IFN-γ+/CD3+IFN-γ+ ratio (r = − 0.845, P < 0.001). IFN-γ secreted by CD3+CD8 + T cells is an important source of serum IFN-γ in TAK patients.


2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi102-vi102
Author(s):  
Herui Wang ◽  
Rogelio Medina ◽  
Juan Ye ◽  
Pashayar Lookian ◽  
Ondrej Uher ◽  
...  

Abstract Despite numerous therapeutic advances, the treatment of glioblastoma multiforme (GBM) remains a challenge, with current 5-year survival rates estimated at 4%. Multiple characteristic elements of GBM contribute to its treatment-resistance, including its low immunogenicity and its highly immunosuppressive microenvironment that can effectively disarm adaptive immune responses. Hence, therapeutic strategies that aim to boost T-lymphocyte mediated responses against GBM are of great therapeutic value. Herein, we present a therapeutic vaccination strategy that promotes the phagocytosis of tumor cells, enhances tumor antigen presentation, and induces a tumor-specific adaptive immune response. This strategy consists of vaccinations with irradiated whole tumor cells (rWTC) pulsed with phagocytic agonists (Mannan-BAM), TLR ligands [LTA, Poly (I:C), and R-848], and anti-CD40 antibody (collectively abbreviated as rWTC-MBTA). We evaluated the therapeutic efficacy of rWTC-MBTA strategy in a mouse syngeneic GL261 orthotopic GBM tumor model. rWTC-MBTA or vehicle control were administered subcutaneously over the right foreleg three days after intracranial injection of GL261 cells. Complete regression (CR) of intracranial tumors was achieved in 70% (7/10) of rWTC-MBTA treated animals while none survived in the control group. Immunophenotyping analyses of peripheral lymph nodes and brain tumors of rWTC-MBTA treated mice demonstrated: (1) increased mature dendritic cells and MHC II+ monocytes; (2) increased effector (CD62L-CD44+) CD4-T and CD8-T cells; (3) increased cytotoxic IFNγ-, TNFα-, and granzyme B-secreting CD4-T and CD8-T cells. Of note, the therapeutic efficacy of rWTC-MBTA disappeared in CD4-T and/or CD8-T lymphocyte depleted mice. Three mice that achieved CR were rechallenged with 50k GL261 cells intracranially 14 months after the last rWTC-MBTA treatment and all rechallenged animals resisted GL261 tumor development, confirming the establishment of long-term immunological memory against GL261 tumor cells. Collectively, our study demonstrated that rWTC-MBTA strategy can effectively activate antigen presenting cells and induce more favorable T-cell signatures in the GBM tumors.


1986 ◽  
Vol 164 (1) ◽  
pp. 363-368 ◽  
Author(s):  
S H Kaufmann ◽  
E Hug ◽  
G De Libero

Lyt-2+ T cell clones were established from Listeria monocytogenes-infected mice. The clones secreted IFN-gamma after stimulation with spleen cells from L. monocytogenes-infected mice plus IL-2. Spleen cells from normal mice were not stimulatory. Furthermore, cloned T cells lysed L. monocytogenes-infected macrophages. Cytolysis was antigen-specific and H-2K-restricted. These findings suggest a role for specific cytotoxic T cells in the immune response to intracellular bacteria.


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