scholarly journals Multiple pathways of T-T interaction in the generation of cytotoxic T lymphocytes to alloantigens.

1980 ◽  
Vol 151 (5) ◽  
pp. 1125-1138 ◽  
Author(s):  
R B Corley ◽  
K A Switzer ◽  
D E Hudson ◽  
M A Cooley
Keyword(s):  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Cell Types ◽  
Mixed Lymphocyte Culture ◽  
Lymphocyte Culture ◽  
Cytotoxic Lymphocytes ◽  
T Helper ◽  
Th Cells ◽  
Peripheral T Cells ◽  
The Difference

The interaction of T helper (Th) cells with syngeneic and allogeneic cytotoxic T lymphocyte precursors (CTL.P) has been investigated. Unprimed and mixed lymphocyte culture-primed peripheral T cells were used as a source of Th. Thymocytes, which depend upon exogenous Th cells for activation, were used as a source of cytotoxic precursors. Data is presented that demonstrates that at least two pathways of T-T interaction can lead to the activation of cytotoxic lymphocytes. The first is an allogeneic effect, in which Th cells recognize and respond to alloantigens expressed on CTL.P. The second is the interaction of Th cells with syngeneic CTL.P, in which both cell types are thought to respond to alloantigens on stimulator cells. The latter interaction can be shown to be restricted by H-2-linked determinants when primed Th cells are used and allogeneic effects against thymocytes are minimized. Restricted interactions between unprimed Th cells and thymocyte CTL.P have never been observed. Mechanisms that may explain the difference between the interaction of unprimed and primed Th cells with CTL.P are discussed.

scholarly journals Heterogeneity in the development of cytotoxic T lymphocytes in vitro revealed by sensitivity to hydrocortisone.

1975 ◽  
Vol 142 (3) ◽  
pp. 790-795 ◽  
Author(s):  
A Altman ◽  
I R Cohen
Keyword(s):  
Cytotoxic T Lymphocytes ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Mixed Lymphocyte Culture ◽  
Lymphocyte Culture ◽  
Differential Sensitivity ◽  
Effector Cells ◽  
In Vitro Systems

In the present study we used hydrocortisone (HC) treatment in vivo as a probe to analyze two different in vitro systems for the regeneration of cytotoxic T lymphocyte (CTL), namely the antifibroblast reaction (AFR) and the mixed lymphocyte culture (MLC) system. We found that cells remaining in the thymus after HC treatment had increased reactivity in these two systems. However, the same treatment in the spleen severely depressed the MLC reactivity in both the proliferative and the cytolytic phases, while markedly increasing the AFR reactivity. These findings demonstrate heterogeneity of CTL precursors and/or their pathways of differentiation into effector cells. In addition, MLC-reactive cells in the thymus appear to be distinct from such cells in the spleen, as judged from their differential sensitivity to HC.

scholarly journals The 3′ CCACCA Sequence of tRNAAla(UGC) Is the Motif That Is Important in Inducing Th1-Like Immune Response, and This Motif Can Be Recognized by Toll-Like Receptor 3

2006 ◽  
Vol 13 (7) ◽  
pp. 733-739 ◽  
Author(s):  
Zhijun Wang ◽  
Li Xiang ◽  
Junjie Shao ◽  
Zhenghong Yuan
Keyword(s):  
Immune Responses ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Hepatitis B Surface Antigen ◽  
Toll Like Receptor ◽  
Anticodon Loop ◽  
T Helper ◽  
D Loop ◽  
Th 1 ◽  
Ctl Responses

ABSTRACT In this article, the immunogenicity of tRNA and the recognition of tRNA by Toll-like receptors (TLRs) are analyzed. Analyses of the effects of different tRNAAla(UGC) fragments (tRNAAla1-76 [corresponding to positions 1 through 76], tRNAAla26-76, tRNAAla40-76, tRNAAla62-76, tRNAAla1-70, tRNAAla26-70, tRNAAla40-70, and tRNAAla62-70) on the immune responses of hepatitis B surface antigen (HBsAg) were performed with BALB/c mice. Results show that tRNAAla1-76, tRNAAla26-76, tRNAAla40-76, and tRNAAla62-76 adjuvants not only induced stronger T helper (Th) 1 immune responses but also cytotoxic-T-lymphocyte (CTL) responses relative to tRNAAla1-70, tRNAAla26-70, tRNAAla40-70, and tRNAAla62-70 adjuvants in HBsAg immunization. A deletion of the D loop (tRNAAla26-76), anticodon loop (tRNAAla40-76), or TψC (tRNAAla62-76) loop of tRNAAla(UGC) does not significantly decrease the adjuvant characteristic of tRNAAla(UGC). However a deletion of the 3′-end CCACCA sequence (tRNAAla1-70, tRNAAla26-70, tRNAAla40-70, and tRNAAla62-70) of tRNAAla(UGC) significantly decreased the adjuvant characteristic in Th1 and CTL immune responses. Moreover, the recognitions of different tRNAAla(UGC) fragments by TLR3, TLR7, TLR8, and TLR9 were analyzed. Results show that a deletion of the 3′ CCACCA sequence of tRNAAla(UGC) significantly decreased the recognition by TLR3. We concluded that the 3′ CCACCA sequence of tRNAAla(UGC) is the important motif to induce Th1 and CTL responses and this motif can be effectively recognized by TLR3.

scholarly journals Cytotoxic T-lymphocyte antigen-4 inhibits GATA-3 but not T-bet mRNA expression during T helper cell differentiation

Immunology ◽  
2006 ◽  
Vol 117 (3) ◽  
pp. 358-367 ◽  
Author(s):  
Francesca Nasta ◽  
Vanessa Ubaldi ◽  
Luigia Pace ◽  
Gino Doria ◽  
Claudio Pioli
Keyword(s):  
Cell Differentiation ◽  
Mrna Expression ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
T Helper Cell ◽  
Helper Cell ◽  
T Helper ◽  
Lymphocyte Antigen

scholarly journals Haplotype-specific suppression of cytotoxic T cell induction by antigen inappropriately presented on T cells.

1983 ◽  
Vol 157 (1) ◽  
pp. 141-154 ◽  
Author(s):  
P J Fink ◽  
I L Weissman ◽  
M J Bevan
Keyword(s):  
T Cells ◽  
Cytotoxic T Lymphocyte ◽  
Mixed Lymphocyte Culture ◽  
Lymphocyte Culture ◽  
Cytotoxic T Cell ◽  
Spleen Cells ◽  
Specific Suppression ◽  
Veto Cells

To detect a strong cytotoxic T lymphocyte (CTL) response to minor histocompatibility (H) antigens in a 5-d mixed lymphocyte culture, it is necessary to use a responder that has been primed in vivo with antigen-bearing cells. It has previously been shown that minor-H-specific CTL can be primed in vivo both directly by foreign spleen cells and by presentation of foreign minor H antigens on host antigen-presenting cells. This latter route is evident in the phenomenon of cross-priming, in which H-2 heterozygous (A x B)F1 mice injected 2 wk previously with minor H-different H-2A (A') spleen cells generate both H-2A- and H-2B-restricted minor-H-specific CTL. In a study of the kinetics of direct- vs. cross-priming to minors in F1 mice, we have found that minor H-different T cells actually suppress the induction of virgin CTL capable of recognizing them. CTL activity measured from F1 mice 3-6 d after injection with viable A' spleen cells is largely H-2B restricted. The H-2A-restricted response recovers such that roughly equal A- and B-restricted activity is detected in mice as early as 8-10 d postinjection. This temporary hyporeactivity does not result from generalized immunosuppression--it is specific for those CTL that recognize the foreign minor H antigen in the context of the H-2 antigens on the injected spleen cells. The injected spleen cells that mediate this suppression are radiosensitive T cells; Lyt-2+ T cells are highly efficient at suppressing the induction of CTL in vivo. No graft vs. host reaction by the injected T cells appears to be required, as suppression of direct primed CTL can be mediated by spleen cells that are wholly tolerant of both host H-2 and minor H antigens. Suppression cannot be demonstrated by in vitro mixing experiments. Several possible mechanisms for haplotype-specific suppression are discussed, including inactivation of responding CTL by veto cells and in vivo sequestration of responding CTL by the injected spleen cells.

scholarly journals H-2-controlled suppression of T cell response to lactate dehydrogenase B. Characterization of the lactate dehydrogenase B suppressor pathway.

1982 ◽  
Vol 156 (3) ◽  
pp. 822-833 ◽  
Author(s):  
C N Baxevanis ◽  
N Ishii ◽  
Z A Nagy ◽  
J Klein
Keyword(s):  
Lactate Dehydrogenase ◽  
T Cell ◽  
Cell Response ◽  
Cell Types ◽  
T Cell Response ◽  
T Helper ◽  
Th Cells ◽  
Th Cell ◽  
Antigen Presenting

We characterized the cell types involved in the H-2-controlled suppression of T cell response to lactate dehydrogenase B (LDHB). The suppressor effector (Tse) was found to be an Lyt-1+2+, J+ cell that recognizes antigen together with Ek molecules of antigen-presenting cells (APC). To become functional, the Tse cell requires a second signal from a nonspecific, Lyt-1+2-, J+ suppressor-inducer (Tsi) cell. The Tsi-Tse interaction is not subject to any genetic restriction. The target cell of suppression is an Lyt-1+2-, J- (most likely T helper [Th]) cell that recognizes LDHB in the context of A molecules on APC. The suppression is manifested in inhibition of the antigen-specific, A-restricted proliferation of Th cells. The interaction between Tse and Th is restricted by the A region of the H-2 complex. Because this restriction is determined by the receptor of Th cells, the mechanism of Th-Tse interaction most likely involves a concomitant recognition of LDHB and A region-controlled molecules by Th cells on the surface of Tse cells.

scholarly journals Changes in the phenotype of peripheral blood lymphocytes from healthy individuals and patients with ischemic heart disease in exogenous hyperhomocysteinemia

2020 ◽  
pp. 87-92
Author(s):  
Е.В. Фефелова ◽  
П.П. Терешков ◽  
Н.Н. Цыбиков ◽  
М.В. Максименя
Keyword(s):  
Cell Culture ◽  
Heart Disease ◽  
Healthy Volunteers ◽  
T Lymphocyte ◽  
Culture Medium ◽  
Cytotoxic Lymphocytes ◽  
T Helper ◽  
Homocysteine Thiolactone ◽  
Blood Samples ◽  
High Doses

Цель исследования - изучение изменения фенотипа лимфоцитов периферической крови под влиянием гомоцистеина и гомоцистеина-тиолактона в краткосрочной культуре клеток. Методика. Исследована венозная кровь 15 относительно здоровых, некурящих добровольцев - мужчин в возрасте 30 - 40 лет и 16 больных ишемической болезнью сердца (стабильная стенокардия 2-го функционального класса), сопоставимых по возрасту с донорами. Кровь брали из локтевой вены в пробирки с добавлением антикоагулянта гепарина Li. В 3 стерильные пластиковые пробирки, содержащие по 1 мл крови, добавляли по 1 мл культуральной среды RPMI-1640 (Miltenyi BiotecGmbH, Германия) с 10% содержанием сыворотки, в 2 из них вносили растворы либо гомоцистеина (50 мкмоль/л), либо гомоцистеин-тиолактона (50 нмоль/л). 3-я и 4-я (контрольные) пробирки содержали эквивалентный объем физиологического раствора или культуральной среды. Фенотип лейкоцитов определяли после 4-часовой инкубации в 4,8% СО2 при 37 ºС. Результаты. Общее количество лейкоцитов, моноцитов и нейтрофилов в исследуемых группах не имело значимых различий. Было зафиксировано лишь увеличение содержания лимфоцитов в образцах периферической крови больных ишемической болезнью сердца за счет увеличения числа всех субпопуляций лимфоцитов. При изучении фенотипа лимфоцитов в культуре под воздействием высоких доз гомоцистеина и гомоцистеин-тиолактона количественные сдвиги наблюдались только в субпопуляции Т-лимфоцитов: в образцах крови условно здоровых добровольцев наблюдалось снижение количества Т-лимфоцитов за счет фракции Т-хелперов. В пробах больных ишемической болезнью сердца под воздействием гипергомоцистеинемии число Т-лимфоцитов не имело значимых различий по сравнению с контролем, но при этом содержание Т-хелперов снижалось на 20%, так же как в образцах крови условно здоровых добровольцев. Уровень цитотоксических лимфоцитов при добавлении гомоцистеина в культуру клеток условно здоровых добровольцев увеличивался на 50%, а при добавлении гомоцистеин-тиолактона - практически в 2 раза, в то же время у больных ишемической болезнью сердца эта фракция лимфоцитов увеличивалась на 70% как под воздействием гомоцистеина, так и гомоцистеин-тиолактона. Заключение. Высокие дозы гомоцистеина снижают количество Т-хелперов и увеличивают число цитотоксических лимфоцитов. Изменения более выражены в образцах крови лиц, страдающих атеросклерозом. Механизмы развития данного феномена требуют дальнейшего изучения. Aim. To study changes in the phenotype of peripheral blood lymphocyte induced by homocysteine and homocysteine thiolactone in a short-term cell culture. Methods. Venous blood was obtained from 15 conventionally healthy, non-smoking male volunteers aged 35.4 ± 4.7 years and 16 patients with ischemic heart disease (functional class II stable angina). Blood was collected from the ulnar vein into tubes containing heparin Li as an anticoagulant. Then 1 ml of RPMI-1640 culture medium (Miltenyi BiotecGmbH, Germany) with 10% of serum was added to each of 3 sterile plastic tubes containing 1 ml of blood each. A solution of either homocysteine (50 μmol/l) or homocysteine-thiolactone (50 nmol/l) was added to two of these tubes. The remaining two tubes (control) contained an equivalent volume of saline or the culture medium. The leukocyte phenotype was determined after 4 hours of incubation at 37°C in 4.8% CO2. Results. Total counts of leukocytes, monocytes and neutrophils did not significantly differ between the study groups. Only an increase in lymphocyte count was observed in blood samples from IHD patients due to increases in all lymphocyte subpopulations. Quantitative changes in the phenotype of lymphocytes exposed to high doses of homocysteine and homocysteine thiolactone were found only for the T-lymphocyte subpopulation; in blood samples from conventionally healthy volunteers, the T-lymphocyte count was decreased due to a decrease in the T-helper fraction. In blood samples from IHD patients exposed to hyperhomocysteinemia, the number of T-lymphocytes did not differ from the control. However, the T-helper level was decreased by 20% similar to that in blood samples of healthy volunteers. The level of cytotoxic lymphocytes in the cell culture from conditionally healthy volunteers exposed to homocysteine was increased by 50% and in the culture exposed to homocysteine thiolactone, it practically doubled. In the blood from IHD patients exposed to homocysteine or homocysteine thiolactone, this lymphocyte fraction was increased by 70%. Conclusion. High doses of homocysteine reduced the number of T-helpers and increased the number of cytotoxic lymphocytes. These changes were more pronounced in blood samples from patients with atherosclerosis. Mechanisms of this phenomenon require a further study.

scholarly journals Surface markers of cloned human T cells with various cytolytic activities.

1981 ◽  
Vol 154 (2) ◽  
pp. 569-574 ◽  
Author(s):  
L Moretta ◽  
M C Mingari ◽  
P R Sekaly ◽  
A Moretta ◽  
B Chapuis ◽  
...  
Keyword(s):  
T Cells ◽  
Cytotoxic T Lymphocyte ◽  
Mixed Lymphocyte Culture ◽  
Lymphocyte Culture ◽  
Target Cells ◽  
Surface Markers ◽  
Human T Cells ◽  
Dependent Cell ◽  
Blast Cells ◽  
Ctl Activity

Human T cells stimulated in secondary allogeneic mixed lymphocyte culture (MLC) were cloned under limiting conditions in microculture systems using T cell growth factor and irradiated allogeneic cells. Clones with lytic activity against either phytohemagglutinin-induced blast cells bearing the stimulating alloantigen(s) (cytotoxic T lymphocyte [CTL] activity), L1210 mouse lymphoma cells coated with rabbit antibody (antibody-dependent cell-mediated cytotoxicity [ADCC]), or K562 human target cells were selected, expanded, and then analyzed for different surface markers, including rosette formation with sheep erythrocytes (E rosettes), receptors for the fc portion of IgG or IgM (Fc gamma R and Fc mu R), and a group of antigens recognized by monoclonal antibodies including Ia, 4F2, OKT8,a nd OKT4. All the cytotoxic cells were E rosette+, Ia+ and 4f2+. Expression of Fc gamma R was restricted to the clones active in ADCC. CTL clones were either OKT8+ or OKT8-. Furthermore, three of the OKT8- CTL clones were OKT4+. In addition, some cytolytic clones devoid of specific CTL activity were OKT8+. It thus appears that the claim that human CTL are OKT8+, OKT4-, and Ia- is not supported by the analysis of their phenotype at the clonal level.

scholarly journals T-lymphocyte response to H-2 mutants. I. Proliferation is dependent on Ly 1+2+ cells.

1978 ◽  
Vol 147 (5) ◽  
pp. 1395-1404 ◽  
Author(s):  
P J Wettstein ◽  
D W Bailey ◽  
L E Mobraaten ◽  
J Klein ◽  
J A Frelinger
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
T Lymphocyte ◽  
Mixed Lymphocyte Culture ◽  
Lymphocyte Culture ◽  
Lymphocyte Response ◽  
Lymphocyte Differentiation ◽  
Selective Depletion

We have determined the Ly phenotype of the T lymphocytes which proliferate in response to mutant H-2K and H-2D alloantigens in primary mixed lymphocyte culture. Responder T cells proliferating in reciprocal cultures of H-2d(KdDd) and H-2da(KdDda) lymphocytes were typed Ly 2+ through selective depletion with specific alloantiserum plus complement. Further, B6-Ly 1a lymphocytes proliferating in response to B6-H-2ba and B6-H-2bf stimulators were typed as Ly 1+2+ through similar analysis. These results are discussed with regard to their impact on views of lymphocyte differentiation and factors determining the identity of alloreactive lymphocytes.

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