Number Of Cytotoxic Lymphocytes Research Articles

Deciphering tumor immune microenvironment differences between high-grade serous and endometrioid ovarian cancer to investigate their potential in indicating immunotherapy response

BackgroundOvarian cancer is a significant public health concern with a poor prognosis for epithelial ovarian cancer. To explore the potential of immunotherapy in treating epithelial ovarian cancer, we investigated the immune microenvironments of 52 patients with epithelial ovarian cancer, including 43 with high-grade serous ovarian cancer and 9 with endometrioid ovarian cancer.ResultsFresh tumor tissue was analyzed for genetic mutations and various parameters related to immune evasion and infiltration. The mean stromal score (stromal cell infiltration) in high-grade serous ovarian cancer was higher than in endometrioid ovarian cancer. The infiltration of CD8 T cells and exhausted CD8 T cells were found to be more extensive in high-grade serous ovarian cancer. Tumor Immune Dysfunction and Exclusion scores, T cell exclusion scores, and cancer-associated fibroblasts (CAF) scores were also higher in the high-grade serous ovarian cancer group, suggesting that the number of cytotoxic lymphocytes in the tumor microenvironment of high-grade serous ovarian cancer is likely lower compared to endometrioid ovarian cancer.ConclusionsThe high mean stromal score and more extensive infiltration and exhaustion of CD8 T cells in high-grade serous ovarian cancer indicate that high-grade serous ovarian cancer exhibits a higher level of cytotoxic T cell infiltration, yet these T cells tend to be in a dysfunctional state. Higher Tumor Immune Dysfunction and Exclusion scores, T cell exclusion scores, and CAF scores in high-grade serous ovarian cancers suggest that immune escape is more likely to occur in high-grade serous ovarian cancer, thus endometrioid ovarian cancer may be more conducive to immunotherapy. Therefore, it is crucial to design immunotherapy clinical trials for ovarian cancer to distinguish between high-grade serous and endometrioid ovarian cancer from the outset. This distinction will help optimize treatment strategies and improve outcomes for patients with different subtypes.

Crosstalk between Apoptosis and Cytotoxic Lymphocytes (CTLs) in the Course of Lagovirus Europaeus GI.1a Infection in Rabbits.

Lagovirus europaeus is a single-stranded RNA virus causing an acute fatal disease in wild and domestic rabbits around the world. Studies have shown that the pivotal process impacting the immune response against the disease is apoptosis, registered mainly in hepatocytes and in peripheral blood, together with an increased number of cytotoxic lymphocytes (CTLs). It is known that cytotoxic lymphocytes can induce target cells to undergo apoptosis on the pseudoreceptor pathway, such apoptosis having been found in several acute and chronic viral infections. The study aimed to assess the crosstalk between the apoptosis of peripheral blood lymphocytes and CD8+ T lymphocytes (as CTLs) in rabbits infected with 6 Lagovirus europaeus GI.1a viruses. Sixty rabbits of Polish hybrid breed comprising both sexes and weighing 3.2-4.2 kg were the experimental group, and an identical group was the control. Each of the six GI.1a Lagovirus europaeus viruses was inoculated into ten experimental rabbits. Control rabbits received glycerol as a placebo. Flow cytometric analysis was performed on blood from the study and control group animals for peripheral blood lymphocyte apoptosis and CTL percentage determination. The activation of apoptosis in peripheral blood lymphocytes was recorded from 4 h post inoculation (p.i.) up to 36 h p.i. The percentage of CTLs in the total blood pool decreased from 8 to 36 h p.i. A negative correlation between apoptosis of lymphocytes and the number of CTLs was proven. This may be the first evidence of virus-induced CTL apoptosis in Lagovirus europaeus GI.1a infection.

Unperturbed Cytotoxic Lymphocyte Phenotype and Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients.

Myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) is a debilitating disorder linked to diverse intracellular infections as well as physiological stress. Cytotoxic lymphocytes combat intracellular infections. Their function is attenuated by stress. Despite numerous studies, the role of cytotoxic lymphocytes in ME/CFS remains unclear. Prompted by advances in the understanding of defects in lymphocyte cytotoxicity, the discovery of adaptive natural killer (NK) cell subsets associated with certain viral infections, and compelling links between stress, adrenaline, and cytotoxic lymphocyte function, we reassessed the role of cytotoxic lymphocytes in ME/CFS. Forty-eight patients from two independent cohorts fulfilling the Canada 2003 criteria for ME/CFS were evaluated with respect to cytotoxic lymphocyte phenotype and function. Results were compared to values from matched healthy controls. Reproducible differences between patients and controls were not found in cytotoxic lymphocyte numbers, cytotoxic granule content, activation status, exocytotic capacity, target cell killing, or cytokine production. One patient expressed low levels of perforin, explained by homozygosity for the PRF1 p.A91V variant. However, overall, this variant was present in a heterozygous state at the expected population frequency among ME/CFS patients. No single patient displayed any pathological patterns of cellular responses. Increased expansions of adaptive NK cells or deviant cytotoxic lymphocyte adrenaline-mediated inhibition were not observed. In addition, supervised dimensionality reduction analyses of the full, multidimensional datasets did not reveal any reproducible patient/control discriminators. In summary, employing sensitive assays and analyses for quantification of cytotoxic lymphocyte differentiation and function, cytotoxicity lymphocyte aberrances were not found among ME/CFS patients. These assessments of cytotoxic lymphocytes therefore do not provide useful biomarkers for the diagnosis of ME/CFS.

ХАРАКТЕРИСТИКА IМУННОГО СТАТУСУ У ЖІНОК З ЛАТЕНТНОЮ ПАПІЛОМАВІРУСНОЮ ІНФЕКЦІЄЮ ШИЙКИ МАТКИ

Мета дослідження – аналіз змін показників, що характеризують стан імунітету, у жінок з генітальною латентною папіломавірусною інфекцією, часто поєднаною з урогенітальною інфекцією, на початку обстеження та через 6 місяців спостереження.Матеріали та методи. Обстежено жінок репродуктивного віку (від 18 до 45 років, 1200 осіб), що звернулись до гінекологічних відділень Перинатального центру та клінічної лікарні № 18 м. Києва за період з 2011 до 2016 рр. Контрольну групу склали 15 здорових жінок. Дослідження проведено за допомогою таких методів, як: цитологічний, кольпоскопічний, бактеріологічний, методу ПЛР, фенотипування лімфоцитів периферичної крові та статистичних методів.Результати дослідження та їх обговорення. При обстеженні 1200 жінок у 210 (16,0 %) виявлена ДНК вірусу папіломи людини (ВПЛ) за відсутності клінічних та морфологічних ознак інфекції, що свідчило про латентну папіломавірусну інфекцію (ПВІ). З них у 84 – діагностована моноінфекція, у 126 – поєднана папіломавірусна та урогенітальна інфекції (УГІ). Інфікування ВПЛ і вірогідність подальшого розвитку захворювання (елімінація або персистенція вірусу) значною мірою визначається клітинними та гуморальними факторами імунітету. Для з’ясування ролі імунної системи людини при латентній ПВІ проведено фенотипування лімфоцитів периферичної крові з використанням моноклональних антитіл та визначення рівня імуноглобулінів (Ig) А, М, G за методом радіальної імунодифузії на початку обстеження і через 6 місяців. У 140 жінок встановлена транзиторна ПВІ, у 70 – персистуюча.У жінок з латентною ПВІ шийки матки виявлені деякі ознаки вторинної імунної недостатності, що виражалось у зниженні відсотка Т-лімфоцитів та Т-хелперів з одночасним підвищенням кількості цитотоксичних лімфоцитів та природних кілерів (NK) на тлі активації гуморальної ланки імунітету. Супутня УГІ статевих органів підтримувала, а іноді і посилювала виявлені особливості імунореактивності при ПВІ. У жінок з транзиторною ПВІ спостерігалась нормалізація показників клітинного та гуморального імунітету, а подальша персистенція ВПЛ у шийці матки призводила до більш суттєвого пригнічення реакцій не тільки клітинної, а й гуморальної ланок імунітету (зниження кількості NK та імунорегуляторного індексу, рівня IgA).Висновок. Таким чином, у жінок з латентною ПВІ ШМ виявлялись деякі ознаки вторинної імунної недостатності, що виражалось у зниженні відсотку Т-лімфоцитів та Т-хелперів, з одночасним підвищенням кількості цитотоксичних лімфоцитів та природних кілерів на тлі активації гуморальної ланки імунітету.

Cytomegalovirus Infection Is Associated with Expansions of CD8 T Cells and Highly Oligoclonal Vdelta1 Gamma/Delta T Cells in Patients Treated with Dasatinib for Chronic Myelogenous Leukaemia

Abstract Dasatinib is a Src family kinase inhibitor and is widely used in the management of CML. It has been shown to have immunosuppressive effects in vitro and clinical use is associated with the development of CD8 T cell and Natural Killer cell expansions that can lead to lymphocytosis. Interestingly, increased lymphocyte counts have been shown to be associated with improved responses to dasatinib. We measured lymphocyte subsets in 94 patients with CML who were treated with either imatinib or dasatinib and were in at least a complete cytogenetic remission. 55 were treated with imatinib and 39 with dasatinib. The overall lymphocyte count was increased in dasatinib-treated patients, at 2.0 * 109/L versus 1.5 * 109/L. Furthermore, within the dasatinib –treated group, CMV seropositivity was associated with a marked increase in overall lymphocyte count within the dasatinib-treated cohort, at 2.3 * 109/L versus 1.7 * 109/L. CD8+ T cells were also increased within the dasatinib-treated cohort, and CMV seropositivity was associated with a marked further increase in cell count. Indeed, CMV seropositive dasatinib-treated patients had 60% higher CD8 T cell counts compared with imatinib treated CMV-seropositive patients, at 0.5 * 109/L versus 0.3*109/L (p = 0.006). A general linear model showed that both CMV seropositivity (p < 0.001) and dasatinib treatment (p = 0.001) were both associated with increases in CD8 T cell numbers. The most marked changes were seen within the CD45RA+ CD27+ EM group and the CD45RA+ CD27- EM group of CD8 T cells. Here there were double the number of CD45RA+ CD27- CD8 T cell responses in dasatinib-treated CMV seropositive patients compared with those on imatinib (0.24 * 109/L versus 0.11 *109/L, p = 0.01), and a threefold increase in EM CD45RA- CD27- CD8 T cells (0.09 * 109/L versus 0.034 * 109/L, p = 0.05). Dasatinib-treated patients also showed increased functional CMV-specific T cell responses, as measured by IFNg release to CMV peptide pools, at 5.1% of CD8 T cells versus 1.4% (p = 0.019) gd T cell numbers were also increased in patients on dasatinib compared with imatinib. The median gd T cell count was 0.05 * 109/L versus 0.02 * 109/L (p = 0.005) and here CMV seropositivity was also associated with the highest gd T cell count. Further analysis of the gd T cell subset revealed that the majority of the gd T cells in the CMV-seropositive group expressed the atypical Vd1 T cell receptor, as opposed to the Vd2 TCR most commonly found in peripheral blood. The median Vd1 gd T cell count in dasatinib-treated CMV seropositive patients was six times that of those on imatinib, at 0.06 * 109/L versus 0.0097 * 109/L (p = 0.02). A general linear model showed that both dasatinib treatment (p = 0.013) and CMV seropositivity (p = 0.002) were associated with significant increases in the Vd1 gd T cell count. The predominant memory subset in those patients that had expansions was of the CD45RA+ CD27- TEMRA subset. The largest expansions of Vd1 gd T cells were seen in patients who were CMV IgM seropositive and here the Vd1 gd T cell count was threefold higher at 0.16 * 109/L compared with 0.05 * 109/L (p = 0.014). Sorted Vd1 gd T cells from these patients showed specificity for CMV-infected fibroblast monolayers as measured by IFNg release. RACE-PCR was then used to interrogate the T cell repertoire of the Vd1 gd T cell population which was found to be strikingly oligoclonal in all cases. Indeed, in one patient a single clone of Vd1 gd T cells made up 99% of the total Vd1 population. In addition to cellular immune response, the humoral CMV-specific immune response was also increased in patients on dasatinib. CMV seropositive patients on dasatinib had higher CMV-specific IgG titre than those on imatinib, at 20.1 IU/ml versus 16.1 IU/ml (p = 0.048). Furthermore, within the CMV IgG seropositive patients, 4 of 23 dasatinib-treated patients were CMV IgM seropositive at various timepoints on treatment, compared with only 1 of 38 of those on imatinib. CMV infection is known to lead to a marked increase in the number of cytotoxic lymphocytes in the blood of healthy individuals. These data reveal that this effect is augmented by the action of dasatinib, which may potentially act by increasing the level of subclinical viral reactivation. Interestingly, these cytotoxic populations include cells has been shown to have anti-leukaemia properties and may have a role in immune anti-tumour responses. Disclosures No relevant conflicts of interest to declare.

Tumor-associated cytotoxic lymphocytes and macrophages as predictive factors in follicular lymphoma

To evaluate the prognostic significance of tumor-associated cytotoxic lymphocytes and macro-phages, an immunohistochemical study of lymph node biopsies obtained from patients with follicular lymphoma (FL) was carried out. The immunohistochemical survey was performed using anti-granzyme B and anti-CD68 antibodies before the patients received the anti-FL treatment. It was shown that the number of cytotoxic lymphocytes (cytotoxic T lymphocytes and NK cells) in patients with good outcome (group 1, n = 31) was significantly higher (p ≤ 0.05) than in patients with poor outcome (group 2, n = 28). The number of CD68-positive macrophages in tumors with nodular-diffuse type of growth in group 2 was significantly higher (p ≤ 0.01) than in group 1. An increased number of cytotoxic lymphocytes may point to the activation of adaptive immunity that favors the good outcome of the disease. In contrast, an increased number of macrophages was associated with a poor outcome of FL. These data suggest that the parameters of cellular microenvironment can be used as prognostic criteria of the FL outcome. Further investigations are needed for the elucidation of the role of the cellular microenvironment in the FL development.

Prognostic Role Of The Microenvironment In Follicular lymphoma

BackgroundFollicular lymphoma (FL) is characterized by clinical heterogeneity. There is a need for easily quantifiable prognostic biomarkers. No consensus has been achieved regarding the prognostic significance of the microvessel density, number of macrophages and cytotoxic lymphocytes within the tumor. ObjectivesTo characterize the microvessel density, number of macrophages and cytotoxic lymphocytes within tumor tissue using immunohistochemical (IHC) analysis of sections from paraffin blocks of lymph node biopsies in two groups of patients with different clinical courses of FL. Patients and methodsThe study included 59 patients with FL: 39 women (67%) and 20 men (33%). The median age was 53 years (range: 27–83 years). Forty nine patients were observed in the National Research Center for Hematology (Moscow), and 10 patients in Cancer Research Center (Moscow), from April 2001 until May 2011. Group 1, “good outcome”, included 28 patients who were followed for 2 or more years after the therapy, had remission, or developed relapse in five or more years from the start of treatment (late relapse). Group 2, “poor outcome”, included 31 patients who died due to tumor progression in the first 1–2 years from the time of diagnosis, had primary tumor resistance, or developed FL relapse in the first year from the start of treatment (early relapse). Patients in both groups received the same initial treatment with rituximab. Five year OS rate in group 1 was significantly higher than in group 2 (83±7% vs 28±13%; ð=0.03). In all 59 cases the samples for IHC analysis were selected by using a table of random numbers, without knowing to which study group they belonged. Each study parameter (microvessel density, number of cytotoxic lymphocytes and macrophages within a tumor) was evaluated and then assigned to prognostic group 1 or 2.The vascularization of tumor tissue was assessed by IHC on sections from paraffin blocks of tumor lymph node biopsies. CD34 and D2-40 (podoplanin) antibodies were used for the visualization of blood and lymphatic vessels, respectively. CD68 antibody was used to detect activated macrophages. Granzyme B antibody was used to visualize cytotoxic lymphocytes.Morphometric analysis was performed using light microscopy and a Leica digital camera (400x). The pictures were processed by the computer program “VideoTesT-Morphology 5.2” in order to estimate the percentage of vessels in the tumor tissue. IHC specimen evaluation was carried out using a table of random numbers. Number of macrophages and cytotoxic lymphocytes in nodular and nodular-diffuse types of tumor growth was evaluated by light microscopy (400x): the cells were counted in 1 mm2 of tumor tissue, and the number of positive cells was determined in the intrafollicular and interfollicular space. ResultsBlood vessel density and lymph vessel density in group 2 were significantly higher than in group 1 (p=0.03). The cut-off point for blood and lymphatic vessel density in 1 mm2, which differentiates group 1 from group 2, was 0.04. The number of cytotoxic lymphocytes in intrafollicular space, interfollicular space and diffuse area of tumor nodules in group 1 was significantly higher than in group 2 (ð=0.05). The cut-off point for tumor-associated cytotoxic lymphocytes in 1 mm2, which differentiates group 1 from group 2, was 100 (Figure 1). The number of macrophages within tumors with nodular and diffuse growth in group 2 was significantly higher than in group 1 (ð=0.01) (Figure 2). The cut-off point for macrophages in 1 mm2, which differentiates group 1 from group 2, was 250. Statistical analysis were done using JMP ver. 10.0 (SAS, Cary, NC). [Display omitted] [Display omitted] ConclusionOur results demonstrate an association between higher angiogenic activity in the tumor and poor prognosis. A low number of cytotoxic lymphocytes and a high number of macrophages within the tumor were also associated with a poor prognosis. We suggest that these results will help to predict clinical response in FL using rituximab. Disclosures:No relevant conflicts of interest to declare.

Fucoidan effect on mononuclear leukocyte immunophenotype and lymphoid organ morphology in mice

Event Abstract Back to Event Fucoidan effect on mononuclear leukocyte immunophenotype and lymphoid organ morphology in mice Olga V. Lebedinskaya1*, Elena A. Lebedinskaya1 and Nelly K. Akhmatova2 1 Acad. E.A. Wagner Perm State Medical Academy, Russia 2 I.I. Mechnikov Institute for Vaccines and Sera, RAMS, Russia The aim of investigation was to study the fucoidan effect on immunophenotype characteristics of spleen mononuclear leukocytes (ML) and on structure and cell composition of mice lymphoid organs. Fucoidan was administrated to CBA mice in a dose of 200 mg/kg of body weight. Subset structure of lymphocytes isolated from spleen was examined with flow cytometry. ML immunophenotype assay was carried out under the administration of two types of preparation - fucoidan japonica and cidcorideus to splenocyte cultures in a dose of 10 μg/ml. Paraffin sections of lymphoid organs were stained by histological and histochemical methods. Intraperitoneal fucoidan injection evoked 1,5-2-fold increment in natural killers-T cells, by 2-6-fold - the amount of T- and B-lymphocytes, and by 1,5-fold -the number of cytotoxic lymphocytes. Morphological analysis revealed the expansion of thymus lobe cortex, enlargement of periarterial muffs area, lymphoid nodes frequently merging in conglomerates in spleen. Following the introduction each of two fucoidan preparations to ML mice spleen cultures there were observed similar changes in splenocyte: statistically significant increase in amount of NK, NKT-cells, activated T-helpers, B-lymphocytes, and decrease in CD3+ and CD8+ cells. Pronounced TLR expression by cell surface was noted. It was demonstrated that fucoidan modulated the effector activity of innate and adaptive immunity and resulted in lymphoid cell proliferation in primary and secondary lymphoid organs. Its ability to promote Toll-like receptor expression by ML surface seems to be promising for its use in immunotherapy. This work was supported by RFBR grant №11-04-96037r_ural_a and administrative body of Perm Region. Keywords: fucoidan, spleen mononuclear leukocytes, Lymphoid organs, Immunotherapy, morphological analysis Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Host-pathogen interactions Citation: Lebedinskaya OV, Lebedinskaya EA and Akhmatova NK (2013). Fucoidan effect on mononuclear leukocyte immunophenotype and lymphoid organ morphology in mice. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00842 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 20 Jun 2013; Published Online: 22 Aug 2013. * Correspondence: Ms. Olga V Lebedinskaya, Acad. E.A. Wagner Perm State Medical Academy, Perm, Russia, lebedinska@mail.ru Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Olga V Lebedinskaya Elena A Lebedinskaya Nelly K Akhmatova Google Olga V Lebedinskaya Elena A Lebedinskaya Nelly K Akhmatova Google Scholar Olga V Lebedinskaya Elena A Lebedinskaya Nelly K Akhmatova PubMed Olga V Lebedinskaya Elena A Lebedinskaya Nelly K Akhmatova Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Increased cytotoxic T cells with effector phenotype in aplastic anemia and myelodysplasia

We hypothesized that an active autoimmune process in aplastic anemia (AA) corresponds to the expansion of cytotoxic lymphocytes (CTLs) displaying mature effector phenotype. We determined whether the numbers of effector CTLs in blood of patients with bone marrow failure syndromes are elevated and correlate with the disease activity and responsiveness to immunosuppression. We analyzed samples from patients with AA, myelodysplastic syndrome (MDS), polytransfused patients with nonimmune-mediated hematologic disease, and normal controls for the presence of effector T lymphocytes using four-color flow cytometry. Expression of CD57 and loss of CD28 on CD8+CD3+ CTL were used as markers for the terminal effector phenotype. In addition, intracellular staining for perforin and granzyme B was preformed. The numbers of effector CTL did not differ between healthy individuals and hematologic controls and the two groups were pooled. The percentages of CD8+CD28- and CD8+CD28-CD57+ cells were significantly higher in AA and MDS patients than in controls. There was a trend toward a gradual decrease in the effector CTLs from the high values observed in untreated new patients and patients who did not respond to immunosuppression, intermediate levels for partial responders and complete responders, to the lowest levels seen in controls. However, severity of pancytopenia did not correlate with the size of the effector cell population. In contrast to CD57+ CTLs, expression of perforin or granzyme B in the cytotoxic effector cells did not differ in AA patients from those of controls. Our results indicate that phenotypically defined effector CTLs are increased in AA and MDS and the effector phenotype may be useful to isolate and characterize antigen-specific T cells in AA in order to delineate the possible inciting or driving agents in AA.

Transplantation antigen expression on murine trophoblast detection by induction of specific alloimmunity

Cell-mediated immune responses to murine embryonic trophoblast cells were investigated using lymphocyte trophoblast cultures (LTC) and cell-mediated lympholysis (CML). Spleen cells from CBA (H-2 k) or C57BL/6 (H-2 b) mice hyperimmunized with 3.5-day-old Balb/c (H-2 d) blastocysts did not undergo DNA synthesis after in vitro exposure to Balb/c blastocyst outgrowths nor were cytotoxic lymphocytes (CTL) generated against H-2 d alloantigens. Splenocytes from Balb/c mice presensitized with semiallogeneic (Balb/c female × C57BL/6 male) trophoblast cells derived from 17- to 20-day placental tissue expressed a weak proliferative response in the presence of semiallogeneic placental trophoblast and produced a moderate number of CTL against H-2 b (paternal strain) alloantigens when compared to mixed lymphocyte cultures (MLC) between Balb/c responder and semiallogeneic (stimulator) spleen cells. CTL were also generated in vitro after splenocytes from Balb/c mice hyperimmunized with semiallogeneic spleen cells were restimulated in vitro with placental trophoblast cells. These studies showing that early-stage trophoblast cells fail to evoke transplantation immunity and placental trophoblast is capable of generating alloimmunity only after combined in vivo hyperimmunization with in vitro restimulation suggest that these trophoblast cells are poorly immunogenic due in part to the relatively weak functional expression of major transplantation antigens.

CORTICOSTEROIDS IN HUMAN LYMPHOCYTE-MEDIATED CYTOTOXIC REACTIONS

The present experiments tested the ability of hydrocortisone and methylprednisolone to alter the process of in vitro generation of cytotoxic T lymphocytes against specific alloantigens or to suppress the lytic phase of the subsequent cytotoxic reactions. The continuous presence of hydrocortisone in culture reduced the total number of cytotoxic lymphocytes recovered following their sensitization in mixed leukocyte cultures. However, corticosteroids had no direct effect on the processes required for generation of cytotoxic lymphocytes, since equal numbers of effector lymphocytes generated in the presence or absence of hydrocortisone produced equivalent, specific lympholysis. The addition of either hydrocortisone or methylprednisolone only during the cytolytic phase of cell-mediated lympholysis failed to significantly suppress the killing of lymphocyte targets. In contrast, parallel studies of the capacity of the same lymphocytes to serve as effector cells in antibody-dependent cellular cytotoxicity showed that both hydrocortisone and methylprednisolone directly inhibited the killing of Chang liver cells sensitized with low concentrations of antibody.