scholarly journals Alternative pathways of T lymphocyte activation.

1978 ◽  
Vol 148 (3) ◽  
pp. 829-834 ◽  
Author(s):  
F H Bach ◽  
B J Alter

Data presented in this paper suggest that there may be two alternative pathways which T lymphocytes can use in generating a cytotoxic response to alloantigens in vitro. First, there is the pathway taken when stimulator and responder cells differ by an entire H-2 complex where Ly1+2- helper T lymphocytes respond to I region encoded lymphocyte defined differences and provide help to the Ly1-2+ cytotoxic T lymphocytes responsive primarily to K/D region encoded cytotoxicity defined determinants. Second, there is the pathway taken when stimulator and responder cells differ by only K or D region differences without an I region encoded difference; under these conditions, an Ly1+2+ cell, which does not appear to play a significant role in the development of a cytotoxic response to an entire H-2 difference, appears to play a pivotal role.

1974 ◽  
Vol 140 (3) ◽  
pp. 703-717 ◽  
Author(s):  
Jean-Charles Cerottini ◽  
Howard D. Engers ◽  
H. Robson MacDonald ◽  
K. Theodor Brunner

Mouse cytotoxic T lymphocytes (CTL) were generated in mixed leukocyte cultures (MLC) using spleen cells as responding cells and irradiated allogeneic spleen cells as stimulating cells. Cytotoxicity was assessed by a quantitative 51Cr assay system and the relative frequency of CTL in individual cell populations was estimated from dose-response curves. Inclusion of 2-mercaptoethanol in the MLC medium resulted in a 20–40-fold increase in the relative number of CTL generated at the peak of the response. Under these culture conditions, cell-mediated cytotoxic activity was detectable in MLC populations as early as 48 h after the onset of the cultures. When spleen cells from mice immunized with allogeneic tumor cells 2–4 mo previously were cultured with irradiated spleen cells of the same alloantigenic specificity (MLC-Imm), it was found that the cell-mediated cytotoxic response was detectable earlier and reached higher levels than that observed in a primary MLC. At the peak of the response, MLC-Imm populations were observed to lyse up to 50% of the target cells within 3 h at a lymphocyte: target cell ratio of 0.3:1. Immunological and physical characterization of the effector cells generated in MLC-Imm indicated that they were medium to large-sized T lymphocytes. Altogether, these studies suggested the existence of an anamnestic cell-mediated cytotoxic response in MLC-Imm.


PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0255574
Author(s):  
Lotte Lindgreen Eriksen ◽  
Morten Aagaard Nielsen ◽  
Tea Lund Laursen ◽  
Bent Deleuran ◽  
Hendrik Vilstrup ◽  
...  

Objectives In alcoholic hepatitis (AH), dysfunctional T lymphocytes may contribute to the high mortality from infections. T lymphocyte activation is governed by the expression of co-stimulatory receptors such as 4-1BB balanced by inhibitory receptors such as Programmed Death receptor 1 (PD-1). 4-1BB expression is unaccounted for in AH, while PD-1 is elevated. We characterized expression of 4-1BB and PD-1 and the associated T lymphocyte functional status in AH and investigated whether these were associated with short-term mortality. Methods Thirty-five patients with AH (at diagnosis and days 7 and 90) were compared with healthy controls (HC). Spontaneous and in vitro stimulated receptor expression were quantified by flow cytometry, and plasma proteins by ELISA. Results At diagnosis, the patients showed increased stimulated 4-1BB responses of CD4+ T lymphocytes. Also, the frequencies of PD-1+ T lymphocytes both with and without co-expressed 4-1BB were increased. Further, interferon-gamma was predominantly produced in T lymphocytes co-expressing 4-1BB. A decrease in the frequency of spontaneous 4-1BB+ T lymphocytes and an increase in soluble 4-1BB during the first week after diagnosis were associated with higher mortality at day 90 in AH. PD-1 expression showed no systematic dynamics related to mortality. Conclusions We found an increased stimulated 4-1BB response of T lymphocytes in AH and early loss of these lymphocytes was associated with a higher short-term mortality. This suggests a role of T lymphocyte 4-1BB expression in the progression of AH.


2010 ◽  
Vol 394 (3) ◽  
pp. 633-638 ◽  
Author(s):  
Li Sun ◽  
Beihua Kong ◽  
Xiugui Sheng ◽  
Jim Jinn-Chyuan Sheu ◽  
Ie-Ming Shih

1986 ◽  
Vol 164 (3) ◽  
pp. 962-967 ◽  
Author(s):  
M F Luciani ◽  
J F Brunet ◽  
M Suzan ◽  
F Denizot ◽  
P Golstein

At least some long-term in vitro-cultured cytotoxic T cell clones and uncloned cell populations are able, in the presence of Con A, to lyse other cells, to be lysed by other cells, but not to lyse themselves. This as-yet-unexplained result may have implications as to the mechanism of T cell-mediated cytotoxicity.


1981 ◽  
Vol 153 (4) ◽  
pp. 871-882 ◽  
Author(s):  
H Y Tse ◽  
J J Mond ◽  
W E Paul

For the purpose of examining more closely the interaction between T and B lymphocytes, we have developed an in vitro T lymphocyte-dependent B lymphocyte proliferation assay. Proliferation of B lymphocytes in response to antigen was found to depend on the presence of primed T lymphocytes; the B lymphocytes could be derived from nonprimed animals. It appears that these B cells were nonspecifically recruited to proliferate. This nonspecific recruitment, however, was found to be Ir-gene restricted in that B lymphocytes from B10.S mice, which are genetic nonresponders to the polymer Glu60-Ala30-Tyr10 (GAT), could not be stimulated by GAT-primed (responder X nonresponder) F1 T cells. The apparent lack of antigen specificity in the face of Ir gene-restricted T-B interaction may have important implications in our understanding of the recognition unit(s) on T lymphocytes.


Gut ◽  
1999 ◽  
Vol 45 (3) ◽  
pp. 382-388 ◽  
Author(s):  
S D Hearing ◽  
M Norman ◽  
C S J Probert ◽  
N Haslam ◽  
C M Dayan

BACKGROUNDUp to 29% of patients with severe ulcerative colitis (UC) fail to respond to steroid treatment and require surgery. Previous studies have failed to show a clear correlation between failure of steroid treatment in severe UC and measures of disease severity. The reasons for treatment failure therefore remain unknown.AIMTo investigate the hypothesis that patients with severe UC who fail to respond to steroid treatment have steroid resistant T lymphocytes.METHODSEighteen patients with severe UC were studied. After seven days’ treatment with high dose intravenous steroids they were classified as complete responders (CR), incomplete responders (IR), or treatment failures (TF). Within 48 hours of admission blood was taken and the antiproliferative effect of dexamethasone on phytohaemagglutinin stimulated peripheral blood T lymphocytes was measured. Maximum dexamethasone induced inhibition of proliferation (Imax) was measured.RESULTSIn vitro T lymphocyte steroid sensitivity of TF and IR patients was significantly less than that of CR patients. Both TF and 3/5 IR patients had an Imax of less than 60%; all CR patients had an Imax of greater than 60%. No significant correlation was seen between response to treatment and disease severity on admission. When in vitro T lymphocyte steroid sensitivity was remeasured three months later, there was no difference between the groups.CONCLUSIONSResults suggest that T lymphocyte steroid resistance is an important factor in determining response to steroid treatment in patients with severe UC and may be more predictive of outcome than disease severity.


2011 ◽  
Vol 19 (1) ◽  
pp. 45-52 ◽  
Author(s):  
Alexandre S. de Almeida ◽  
Christina T. Fiske ◽  
Timothy R. Sterling ◽  
Spyros A. Kalams

ABSTRACTExtrapulmonary tuberculosis may be due to underlying immune compromise. Immunosuppressive regulatory T cells (Treg cells), and CD4+T lymphocytes in general, are important in the host immune response toMycobacterium tuberculosis. We evaluated T lymphocytes from patients after recovery from extrapulmonary tuberculosis, which may reflect conditions beforeM. tuberculosisinfection. A case-control study was conducted among HIV-uninfected adults with previously treated extrapulmonary tuberculosis and 3 sets of controls: (i) subjects with previously treated pulmonary tuberculosis, (ii) close tuberculosis contacts withM. tuberculosisinfection, and (iii) close tuberculosis contacts with no infection. Monocyte-depleted peripheral blood mononuclear cells (PBMC-M) were stained for CD4+CD25hiCD127lowFoxP3+cell (Treg cell) and T lymphocyte activation. Both characteristics were compared as continuous variables between groups with the Kruskal-Wallis test. There were 7 extrapulmonary tuberculosis cases, 18 pulmonary tuberculosis controls, 17 controls withM. tuberculosisinfection, and 18 controls withoutM. tuberculosisinfection. The median Treg cell proportion was highest among persons with previous extrapulmonary tuberculosis (1.23%) compared to subjects with pulmonary tuberculosis (0.56%), latentM. tuberculosisinfection (0.14%), or noM. tuberculosisinfection (0.20%) (P= 0.001). The median proportion of CD4+T lymphocytes that expressed the activation markers HLA-DR and CD38 was highest for CD4+T lymphocytes from persons with previous extrapulmonary tuberculosis (0.79%) compared to subjects with pulmonary tuberculosis (0.44%), latentM. tuberculosisinfection (0.14%), or noM. tuberculosisinfection (0.32%) (P= 0.005). Compared with controls, persons with previously treated extrapulmonary tuberculosis had the highest Treg cell frequency, but also the highest levels of CD4+T lymphocyte activation. Immune dysregulation may be a feature of individuals at risk for extrapulmonary tuberculosis.


2011 ◽  
Vol 74 (2) ◽  
pp. 155-164 ◽  
Author(s):  
D. Teschner ◽  
G. Wenzel ◽  
E. Distler ◽  
E. Schnürer ◽  
M. Theobald ◽  
...  

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