Loss of the ex vivo but not the reinducible CD8+ T-cell response to Tax in human T-cell leukemia virus type 1-infected patients with adult T-cell leukemia/lymphoma.
Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia/lymphoma (ATLL) and HTLV-1-associated myelopathy (HAM). In asymptomatic carriers and HAM patients, HTLV-1 infection leads to a vigorous cytotoxic T-cell (CTL) response mainly directed to the regulatory Tax protein. In contrast, initial studies showed that anti-HTLV-1 CTL activities were not reproductively detected in ATLL patients, neither ex vivo, nor after in vitro restimulation. To better understand this discrepancy, we explored the anti-HTLV-1 CD8+ T-cell response of eight ATLL patients by using in vitro restimulated or freshly isolated CD8+ T cells. In all the ATLL patients, we found that mitogenic activation allowed the induction of CD8+ T cells able to lyse autologous HTLV-1-infected cells and/or to produce IFNgamma in response to Tax peptides. In contrast, only a minority of the patients possessed CD8+ cells able to respond ex vivo to the same epitopes. These findings indicate that although a restimulatable anti-HTLV-1 CTL activity persists during ATLL, the specific ex vivo response is not constantly maintained. This provides definitive evidence that the CD8+ T-cell response to HTLV-1 is affected by ATLL development and reveals that a major defect concerns the generation and/or the functionality of CD8+ effectors.
Service d'Hématologie and Centre National de la Recherche Scientifique, UMR 8603, Hôpital Necker, Paris, France.
B
B
Arnulf
M
M
Thorel
Y
Y
Poirot
R
R
Tamouza
E
E
Boulanger
A
A
Jaccard
E
E
Oksenhendler
O
O
Hermine
C
C
Pique
D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D002857:Chromium / Q000378:metabolism; D016356:Gene Products, tax / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000032:analysis; D015481:HTLV-I Antibodies / Q000096:biosynthesis; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000145:classification / Q000276:immunology* / Q000821:virology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D010446:Peptide Fragments / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell / Q000032:analysis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D016356:Gene Products, tax; D015789:HLA-A2 Antigen; D015481:HTLV-I Antibodies; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D002857:Chromium; D007371:Interferon-gamma