Direct activation of CD8+ cytotoxic T lymphocytes by dendritic cells.

Recent experiments (11-13) have shown that antigen-specific, CD8+, CD4- T lymphocytes can be induced to proliferate and become killer cells in the absence of a second population of "helper" CD8-, CD4+ cells. We have studied early events in the activation of CD4+ and CD8+ T cell subsets in the primary mixed leukocyte reaction. Dendritic cells are a major if not essential accessory cell for the activation of both subpopulations. Antigen-bearing macrophages fail to stimulate unprimed CD8+ cells, but act as targets for the sensitized cytolytic lymphocytes that are induced by dendritic cells. The initial proliferative response is comparable for CD4+ and CD8+ lymphocyte subsets. For both subpopulations, dendritic cells efficiently cluster the responding lymphocytes on the first day and induce the release of IL-2. The data indicate that CD4+ and CD8+ lymphocytes can be activated by a similar mechanism, and illustrate the special role of dendritic cells in the sensitization stage of cell-mediated immunity.

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Involvement of CD26 in Differentiation and Functions of Th1 and Th17 Subpopulations of T Lymphocytes

Journal of Immunology Research ◽

10.1155/2021/6671410 ◽

2021 ◽

Vol 2021 ◽

pp. 1-13

Author(s):

Xiangli Zhao ◽

Wenhan Wang ◽

Kai Zhang ◽

Jingya Yang ◽

Hendrik Fuchs ◽

...

Keyword(s):

T Cell ◽

T Lymphocytes ◽

T Cell Activation ◽

Solid Phase ◽

Human Peripheral Blood ◽

T Cell Subsets ◽

Cd4 Cells ◽

Ifn Γ ◽

Cd26 Expression

CD26, acting as a costimulator of T cell activation, plays an important role in the immune system. However, the role of CD26 in the differentiation of T cell subsets, especially of new paradigms of T cells, such as Th17 and Tregs, is not fully clarified. In the present study, the role of CD26 in T cell differentiation was investigated in vitro. CD26 expression was analyzed in the different subsets of human peripheral blood T lymphocytes after solid-phase immobilized specific anti-CD3 mAb stimulation. Here, the percentage of CD4+ cells significantly increased and most of these cells were coexpressed with CD26, suggesting a close correlation of CD26 expression with the proliferation of CD4+ cells. Subsequently, after immobilized anti-CD3 mAb stimulation, CD26 high-expressing cells (CD26high) were separated from CD26 low-expressing cells (CD26low) by magnetic cell sorting. We found that the percentages of cells secreting Th1 typical cytokines (IL-2, IFN-γ) and Th17 typical cytokines (IL-6, IL-17, and IL-22) or expressing Th17 typical biomarkers (IL-23R, CD161, and CD196) in the CD26high group were markedly higher than in those in the CD26low group. In addition, a coexpression of CD26 with IL-2, IFN-γ, IL-17, IL-22, and IL-23R in lymphocytes was demonstrated by fluorescence microscopy. These results provide direct evidence that the high expression of CD26 is accompanied by the differentiation of T lymphocytes into Th1 and Th17, indicating that CD26 plays a crucial role in regulating the immune response.

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The predictive role of lymphocyte subsets and laboratory measurements in COVID-19 disease: a retrospective study

Therapeutic Advances in Respiratory Disease ◽

10.1177/17534666211049739 ◽

2021 ◽

Vol 15 ◽

pp. 175346662110497

Author(s):

Lin Wang ◽

Jun Chen ◽

Jun Zhao ◽

Feng Li ◽

Shuihua Lu ◽

...

Keyword(s):

Mechanical Ventilation ◽

T Cell ◽

Lymphocyte Subsets ◽

Total Lymphocyte Count ◽

Laboratory Measurements ◽

Cd4 Cells ◽

Cd8 Cells ◽

Icu Admission ◽

Predictive Role

Aim: The aim of this study was to investigate the predictive role of lymphocyte subsets and other laboratory measurements in patients with COVID-19. Methods: Electronic medical records of adult patients with confirmed diagnosis of COVID-19 from the Shanghai Public Health Clinical Center were reviewed retrospectively to obtain relevant data. Results: The mean age of patients was 40.98 ± 15.95 years, with 58% of the patients being males. The cutoff values at the intensive care unit (ICU) admission, mechanical ventilation, and mortality were CD4+ cells (267, 198, and 405), CD8+ cells (263, 203, and 182), and CD4+ /CD8+ cells (1.4, 1.8, and 1.4). The cutoffs below these values indicate the higher chances of disease progression. Higher CD4+ cell count led to lesser chances for ICU admission [odds ratio (OR) (95% confidence interval (CI): 0.994 (0.991, 0.997); p = 0.0002] and mortality [OR (95% CI): 0.988 (0.979, 0.99); p = 0.001], higher CD8+ count was an independent risk factor for ICU admission. T-cell count positively correlated with total lymphocyte count and platelets, while negatively correlated with D-dimer and lactate dehydrogenase (LDH). Among patients with non-severe COVID-19, median CD8+ T cell, CD4+ T cell, total lymphocyte count, and platelets were 570, 362, 1.45, and 211, respectively, while median values decreased to 149, 106, 0.64, and 172, respectively, in patients with severe COVID-19. Conclusion: Lower T lymphocyte subsets were significantly associated with higher admission to ICU, mechanical ventilation, and mortality among patients with COVID-19. A cutoff value of ICU admission, mechanical ventilation, and mortality below CD4+ cells (267, 198, and 405), CD8+ cells (263, 203, 182), and CD4+/CD8+ cells (1.4, 1.8, 1.4) may help identify patients at high risk of disease progression. The continuous evaluation of laboratory indices may help with dismal prognosis and prompt intervention to improve outcomes.

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Clonal expansion of human T lymphocytes initiated by dendritic cells.

Journal of Experimental Medicine ◽

10.1084/jem.169.1.315 ◽

1989 ◽

Vol 169 (1) ◽

pp. 315-320 ◽

Cited By ~ 34

Author(s):

E Langhoff ◽

R M Steinman

Keyword(s):

Dendritic Cells ◽

T Cell ◽

T Lymphocytes ◽

Clonal Growth ◽

Human Peripheral Blood ◽

Clonal Expansion ◽

Accessory Cell ◽

Feeder Cell ◽

Cd8 Cells ◽

Cell Clones

The accessory cell requirements for cloning T cells in the presence of lectin and T cell growth factors were examined with cells from human peripheral blood. We found that dendritic cells were active and perhaps essential. Single CD4+ lymphocytes could be cloned with 80% efficiency, and CD8+ cells with 50-60% efficiency if 10(3) syngeneic or allogeneic dendritic cells were added. Some T cell clones developed even with one dendritic cell. Monocytes or B lymphocytes from blood were at least 100-fold weaker in supporting clonal growth. These findings suggest a specialized feeder cell requirement, namely dendritic cells, for cloning T lymphocytes from single resting precursors.

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Private specificities of H-2K and H-2D loci as possible selective targets for effector lymphocytes in cell-mediated immunity.

Journal of Experimental Medicine ◽

10.1084/jem.141.1.11 ◽

1975 ◽

Vol 141 (1) ◽

pp. 11-26 ◽

Cited By ~ 46

Author(s):

B D Brondz ◽

I K Egorov ◽

G I Drizlikh

Keyword(s):

T Lymphocytes ◽

Target Cells ◽

Cell Mediated Immunity ◽

Skin Grafts ◽

Immune Lymphocytes ◽

Direct Cytotoxicity ◽

Cross Absorption ◽

Private Specificity ◽

Two Populations

Receptors of effector T lymphocytes of congeneic strains of mice do not recognize public H-2 specificities and react to private H-2 specificities only. This has been established with the use of three tests: direct cytotoxicity assay of immune lymphocytes upon target cells, specific absorption of the lymphocytes on the target cells, and rejection of skin grafts at an accelerated fashion. Immunization with two private H-2 specificities in the system C57BL/10ScSn leads to B10.D2 induces formation of two corresponding populations of effector lymphocytes in unequal proportion: a greater part of them is directed against the private specificity H-2.33 (Kb), while the smaller part is towards H-2.2 (Db) private specificity. These two populations of effector lymphocytes do not overlap, as demonstrated by experiments on their cross-absorption on B10.D2 (R107), B10.D2 (R101), B10.A(2R), and B10.A(5R) target cells, as well as on mixtures of R107 and R101 targets. Following removal of lymphocytes reacting with one of the private H-2 specificities, lymphocytes specific to the other specificity are fully maintained. A mixture of target cells, each bearing one of the two immunizing private specificities, absorbs 100% of the immune lymphocytes and is totally destroyed by them. It is suggested that H-2 antigens are natural complexes of hapten-carrier type, in which the role of hapten is played by public H-2 specifities and that of the carrier determinant by either private H-2 specificities or structures closely linked to them. Various models of steric arrangement of MHC determinants recognized by receptors of effector T lymphocytes are discussed.

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Short-Term Dietary Intervention with Cooked but Not Raw Brassica Leafy Vegetables Increases Telomerase Activity in CD8+ Lymphocytes in a Randomized Human Trial

Nutrients ◽

10.3390/nu11040786 ◽

2019 ◽

Vol 11 (4) ◽

pp. 786 ◽

Cited By ~ 4

Author(s):

Hoai Tran ◽

Monika Schreiner ◽

Nina Schlotz ◽

Evelyn Lamy

Keyword(s):

T Cell ◽

T Lymphocytes ◽

Healthy Volunteers ◽

Dietary Intervention ◽

Telomerase Activity ◽

Leafy Vegetables ◽

T Cell Subsets ◽

Long Term Effects ◽

Short Term ◽

Cd8 Cells

Telomerase in T lymphocytes is dynamic and limited evidence from epidemiological studies indicates that the enzyme can be modulated in peripheral lymphocytes by dietary and lifestyle factors. The differential effect of dietary intervention on T cell subsets has not been investigated so far. Brassica vegetables are known for their multiple beneficial effects on human health, and here, the effect of a five-day short-term intervention with raw or cooked leaves of Brassica carinata on telomerase activity in CD4+ and CD8+ T cells from 22 healthy volunteers was investigated in a randomized single-blind, controlled crossover study. Blood samples were collected before and after intervention, and CD4+/CD8+ T lymphocytes were isolated. Telomerase activity was quantified using the TRAP-ELISA assay. Intervention with both preparations led to a marginal increase in telomerase activity of CD4+ cells compared to the baseline level. In CD8+ cells, a significant increase in telomerase activity (25%, p < 0.05) was seen after intervention with the cooked material. An increase in telomerase activity in CD8+ cells of healthy volunteers could be regarded as beneficial in terms of helping with the cell-mediated immune response. Whether a Brassica intervention has long-term effects on telomere extension in specific T cell subsets needs to be determined.

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Monoclonal antibodies to LFA-1 and to CD4 inhibit the mixed leukocyte reaction after the antigen-dependent clustering of dendritic cells and T lymphocytes.

Journal of Experimental Medicine ◽

10.1084/jem.165.5.1403 ◽

1987 ◽

Vol 165 (5) ◽

pp. 1403-1417 ◽

Cited By ~ 94

Author(s):

K Inaba ◽

R M Steinman

Keyword(s):

T Cells ◽

Dendritic Cells ◽

T Cell ◽

Cell Mediated Immunity ◽

Lymphocyte Function ◽

Mixed Leukocyte Reaction ◽

Binding Assays ◽

Lymphocyte Blastogenesis ◽

And Function

T cell proliferation in response to many stimuli is known to occur in discrete clusters of dendritic cells (DC) and CD4+ helper lymphocytes. The role of lymphocyte function-associated antigen (LFA-1) and CD4 in the formation and function of these clusters has been evaluated in the mixed leukocyte reaction (MLR). By day 1 of the control MLR, most of the DC and responsive T cells are associated in discrete aggregates. Addition of anti-LFA-1 and CD4 reagents does not block DC-T aggregation but reduces the subsequent proliferative response by 80-90%. Anti-LFA-1 disassembles newly formed DC-T cell aggregates, whereas anti-CD4 inhibits blastogenesis without disrupting the cluster. Binding of DC to sensitized, antigen-specific CD4+ cells has been studied using lymphoblasts isolated at day 4 of the MLR. It has been shown previously that greater than 80% blasts rebind to DC in an antigen-specific fashion in rapid (10 min) binding assays. Antigen-dependent DC-T binding is blocked by anti-Ia but not by mAb to LFA-1 or CD4. However, the bound anti-CD4-coated lymphocytes are unable to release IL-2. Anti-LFA-1-coated T cells release IL-2 but are easily disaggregated after binding to DC. These findings lead to two conclusions. LFA-1 and CD4 are not involved in the initial steps whereby DC bind to T cells but exert an independent and subsequent role. LFA-1 acts to stabilize the DC-T cluster, while CD4 contributes to lymphocyte blastogenesis and IL-2 release. Because DC but not other presenting cells cluster unprimed lymphocytes, it seems likely that an antigen-independent mechanism distinct from LFA-1 and CD4 mediates aggregate formation at the onset of cell-mediated immunity.

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CD4+ but not CD8+ cells are essential for allorejection.

Journal of Experimental Medicine ◽

10.1084/jem.184.5.2013 ◽

1996 ◽

Vol 184 (5) ◽

pp. 2013-2018 ◽

Cited By ~ 238

Author(s):

N R Krieger ◽

D P Yin ◽

C G Fathman

Keyword(s):

Cd8 T Cells ◽

Knockout Mice ◽

Antibody Therapy ◽

Major Histocompatibility ◽

Cd4 Cells ◽

Cd8 Cells ◽

Targeted Gene Disruption ◽

Histocompatibility Complex ◽

Skin Allografts

The generation of knockout mice with targeted gene disruption has provided a valuable tool for studying the immune response. Here we describe the use of CD4 and CD8 knockout mice to examine the role of CD4+ and CD8+ cells in initiating allotransplantation rejection. Pretreatment with a brief course of depletive anti-CD4 monoclonal antibody therapy allowed permanent survival of heart, but not skin, allografts transplanted across a major histocompatibility barrier. However, skin as well as heart grafts were permanently accepted in the CD4 knockout mice. Transfer of CD4+ cells into CD4 knockout recipient mice 1 d before skin engraftment reconstituted rejection, demonstrating that CD4+ cells are necessary for initiating rejection of allogeneic transplants. Major histocompatibility complex disparate heart and skin allografts transplanted into CD8 knockout recipients were rejected within 10 d. This study demonstrates that CD4+ but not CD8+ T cells are absolutely required to initiate allograft rejection.

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Treatment and biology of lymphomatoid granulomatosis

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.8029 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 8029-8029 ◽

Cited By ~ 1

Author(s):

B. R. Healey Bird ◽

N. Grant ◽

K. Dunleavy ◽

J. Janik ◽

J. Cohen ◽

...

Keyword(s):

B Cells ◽

Lymphocyte Subsets ◽

High Dose ◽

Cd4 Cells ◽

Cd8 Cells ◽

Viral Loads ◽

The Mean ◽

Male Sex ◽

Age Range ◽

Grade Iii

8029 Background: LYG is a rare angiocentric-destructive process with EBV+ B-cells and reactive T-cells. LYG is graded with grades I-II showing rare-moderate large EBV+ B-cells (usually polyclonal or oligoclonal) and grade III showing numerous large EBV+ B-cells (usually monoclonal), likely reflecting progressive transformation. Historically, steroids and/or chemotherapy have a 14 mos median survival. Methods: We are investigating Interferon-a (I-a) for grade I/II and dose-adjusted EPOCH ±Rituximab (R) for grade III LYG. Results: Characteristics of 53 pts are: male sex 68%; median age (range) 46 (17–67) and median ECOG P.S. 1 (0–3). Disease sites include lung 98%, CNS 38%, kidney 15%, skin 17%, liver 19% and nodes 4%. On study LYG grades are I-30%, II-26% and III-44%. Prior treatment was none-28%, chemotherapy± R-34%, and steroids alone-40% of pts. For grades I/II, I-a is begun at 7.5 million IUs TIW and escalated as tolerated until disease regression and continued 1 yr after CR. Of 31 patients treated with I-a, PFS is 62% at the median f/u of 5.3 yrs. Of 25 evaluable pts (3 NE; 3 TE), 60% had sustained CR for a median of 60 mos (4–175). In 9 pts who progressed on I-a, grade III was found in 5. Thus, in 20 pts with only grade I/II, 75% had sustained CR with I-a. In 11 evaluable pts with CNS disease, 81% achieved remission with I-a alone. The median time to remission is 9 mos (3–40) and median I-a dose is 20 MIU (7–40). Among 24 pts receiving DA-EPOCH±R, PFS is 40% at the median f/u of 28 mos. Of 21 evaluable pts (2 NE, 1 TE), 66% achieved CR. OS of all 53 pts is 68% at the median f/u of 4 yrs. Median EBV viral loads in 29 pts at study entry were 18 copies/10e6 genome equivalents (0–22727) (normal<200). Lymphocyte subsets in 30 pts showed a median CD4–428 (24–2322) and CD8–165 cells/mm3 (42–1316). In 12 pts in CR and with serial values, the mean CD8 cells (131 ± 44) (p2= 0.013) but not CD4 cells (65 ± 75) increased with treatment. Conclusions: High dose I-a produces sustained remissions in grade I/II LYG and is effective in CNS LYG. DA-EPOCH±R can produce durable CRs in grade III LYG. We hypothesize LYG emerges in a compromised immune milieu and undergoes progressive transformation if not effectively treated. Historical results suggest steroids may allow transformation by compromising immune function. No significant financial relationships to disclose.

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Cellular Mediators of Inflammation: Tregs andTH17Cells in Gastrointestinal Diseases

Mediators of Inflammation ◽

10.1155/2009/132028 ◽

2009 ◽

Vol 2009 ◽

pp. 1-11 ◽

Cited By ~ 21

Author(s):

Franco Pandolfi ◽

Rossella Cianci ◽

Danilo Pagliari ◽

Raffaele Landolfi ◽

Giovanni Cammarota

Keyword(s):

T Regulatory Cells ◽

Suppressor Cells ◽

Gastrointestinal Diseases ◽

The Novel ◽

Cd4 Cells ◽

Suppressor Activity ◽

Cd8 Cells ◽

Mediators Of Inflammation ◽

Cellular Mediators

Human lymphocyte subpopulations were originally classified as T- and B-cells in the 70s. Later, with the development of monoclonal antibodies, it became possible to recognize, within the T-cells, functional populations:CD4+andCD8+. These populations were usually referred to as “helper” and “suppressor” cells, respectively. However several investigations within the CD8 cells failed to detect a true suppressor activity. Therefore the term suppressor was neglected because it generated confusion. Much later, true suppressor activity was recognized in a subpopulation of CD4 cells characterized by high levels of CD25. The novel population is usually referred to as T regulatory cells (Tregs) and it is characterized by the expression of FoxP3. The heterogeneity of CD4 cells was further expanded by the recent description of a novel subpopulation characterized by production of IL-17. These cells are generally referred to asTH17. They contribute to regulate the overall immune response together with other cytokine-producing populations. Treg andTH17cells are related because they could derive from a common progenitor, depending on the presence of certain cytokines. The purpose of this review is to summarize recent findings of the role of these novel populations in the field of human gastroenterological disease.

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