Analysis of T Lymphocytes Cloned from Rejected Kidney Allograft: High Frequency of Cytotoxic T Cell Precursor

1988 ◽  
Vol 1 (3) ◽  
pp. 171-176 ◽  
Author(s):  
R. Benvenuto ◽  
A. Bachetoni ◽  
A. Franco ◽  
P. Cinti ◽  
F. Sallusto ◽  
...  

A high proportion of CD8 positive cells and inverted CD4/CD8 ratio were found in peripheral blood mononuclear cells and in freshly isolated kidney-graft infiltrating cells in two patients who underwent irreversible acute rejection. Seventy seven T cell clones were generated from the T cell blasts infiltrating rejected kidney allografts. The majority of T cell clones obtained showed CD8 phenotype in accordance to uncloned graft infiltrating cells. All clones (both CD8 and CD4) displayed cytolytic activity evaluated by lectin-dependent cell-mediated cytotoxicity and natural killer (NK) activities. None of the clones presented lymphokine activated killer phenomenon. These data suggest that the graft infiltrate is characterized by T cell clones with cytolytic potential and that these T cell clones may be responsible for the killing of graft cells by a CTL or NK type mechanism.

2020 ◽  
Author(s):  
Michael J. Bale ◽  
Mary Grace Katusiime ◽  
Daria Wells ◽  
Xiaolin Wu ◽  
Jonathan Spindler ◽  
...  

AbstractLittle is known about the emergence and persistence of HIV-infected T cell clones in perinatally-infected children. We analyzed peripheral blood mononuclear cells for clonal expansion in 11 children who initiated antiretroviral therapy (ART) between 1.8-17.4 months of age and with viremia suppressed for 6-9 years. We obtained 8,662 HIV-1 integration sites from pre-ART and 1,861 sites on ART. Expanded clones of infected cells were detected pre-ART in 10/11 children. In 8 children, infected cell clones detected pre-ART persisted for 6-9 years on ART. A comparison of integration sites in the samples obtained on ART with healthy donor PBMC infected ex-vivo showed selection for cells with proviruses integrated in BACH2 and STAT5B. Our analyses indicate that, despite marked differences in T cell composition and dynamics between children and adults, HIV-infected cell clones are established early in children, persist for up to 9 years on ART, and can be driven by proviral integration in proto-oncogenes.


Blood ◽  
1998 ◽  
Vol 92 (1) ◽  
pp. 19-24 ◽  
Author(s):  
Marina Ostankovitch ◽  
Agnès Buzyn ◽  
Delphine Bonhomme ◽  
Francine Connan ◽  
Didier Bouscary ◽  
...  

Recent studies have shown that transfusions of HLA-compatible donor lymphocytes may induce complete remission in marrow-grafted patients with relapses of acute myeloblastic leukemia (AML). We investigated the in vitro generation of antileukemia T-cell clones obtained from the peripheral blood mononuclear cells of a partially HLA-compatible donor (HLA-A2 and B7 molecules in common with the leukemic blasts) after stimulation with a pool of naturally processed peptides extracted from leukemic blast cells collected at diagnosis from a patient with hyperleucocytosis AML. We recovered a significant quantity of peptides that bound to the HLA-A2 or HLA-B7 molecules that were able to induce cytolytic T-lymphocyte (CTL) lines and clones specific for the eluted AML peptides and restricted to the HLA-A2 or B7 molecules. Such CTL line did not recognize the patient's nonleukemic cells, and one clone was able to interact with the leukemic blasts from which the naturally processed peptides had been eluted. Such T-cell clones might provide a rationale for the development of adoptive immunotherapy and could be used to improve the efficiency of HLA-compatible T-lymphocyte transfusions and the graft-versus-leukemia response in patients with AML.


1990 ◽  
Vol 171 (6) ◽  
pp. 2011-2024 ◽  
Author(s):  
T H Ottenhoff ◽  
T Mutis

Mycobacterial antigens not only stimulate Th cells that produce macrophage-activating factors, but also CD4+ and CD8+ CTL that lyse human macrophages. The mycobacterial recombinant 65-kD hsp was previously found to be an important target antigen for polyclonal CD4+ CTL. Because of the major role of 65-kD hsp in the immune response to mycobacterial as well as autoantigens, we have studied CTL activity to this protein at the clonal level. HLA-DR or HLA-DQ restricted, CD4+CD8- T cell clones that recognize different peptides of the M. leprae 65-kD hsp strongly lysed EBV-BLCL pulsed with specific but not irrelevant peptide. No bystander lysis of B cells, T cells, or tumor cells was seen. Target cell lysis could not be triggered by PMA + Ca2+ ionophore alone and depended on active metabolism. Interestingly, these CD4+ CTL also strongly lysed themselves and other HLA-class II compatible CD4+ (TCR-alpha/beta or -gamma/delta) or CD8+ CTL clones in the presence of peptide, suggesting that CTL are not actively protected from CTL-mediated lysis. Cold target competition experiments suggested that EBV-BLCL targets were more efficiently recognized than CD4+ CTL targets. These results demonstrate that hsp65 peptide-specific HLA class II-restricted CD4+ T cell clones display strong peptide-dependent cytolytic activity towards both APCs, and, unexpectedly, CD4+ and CD8+ CTL clones, including themselves. Since, in contrast to murine T cells human T cells express class II, CTL-mediated T cell killing may represent a novel immunoregulatory pathway in man.


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.


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