T-cell receptor usage of interleukin-2-responsive peripheral gamma delta T cells.
The majority of human peripheral gamma delta T cells express the V gamma 9 gene in combination with the V delta 2 gene. The diversity of this subset of gamma delta T cells is limited by a preferential usage of the J gamma P gene segment and a highly distinctive junctional motif of the T-cell receptor (TCR) delta chain. We and others have observed that peripheral blood derived V gamma 9+V delta 2+ gamma delta T cells of healthy individuals are activated after stimulation with interleukin-2 (IL-2) in vitro, but only a small percentage of gamma delta T cells subsequently proliferates. To assess whether the proliferating, IL-2-responsive gamma delta T cells represent a selective group of T cells, we have analysed TCR junctional features of IL-2-responsive gamma delta T cells. Out of 30 individuals studied, nine were identified as IL-2-responders and three as IL-2-hyperresponders. The TCR V(D)J gene usage from IL-2 stimulated peripheral blood lymphocytes of these IL-2-(hyper)responsive individuals was analysed. The results showed that in most individuals gamma delta T cells polyclonally expanded after stimulation with IL-2. In two IL-2-hyperresponder individuals, however, a monoclonal expansion of a particular V gamma 9+V delta 2+ gamma delta T cell was found. In one of these individuals, this V gamma 9+V delta 2+ T-cell clone expressed a very rare gamma delta TCR type because of the presence of an Ala within the junctional region at a conserved position relative to V delta framework residues (delta 97), which is very infrequently used by peripheral blood V gamma 9+V delta 2+ cells. This particular clonotype could also be detected in unstimulated PBL samples taken from that individual, and made up for 30% of the total peripheral gamma delta T-cell pool. These data indicate that in general IL-2-responsive V gamma 9+V delta 2+ gamma delta T cells represent a polyclonal population, reflecting in vivo stimulation with multiple antigens or superantigens. In contrast, monoclonal expansions of gamma delta T cells after stimulation with IL-2 can also occur, which may be related to an in vivo stimulation by one particular antigen, rendering this gamma delta T-cell type dominant in the peripheral blood.
Department of Immunohaematology and Bloodbank, University Hospital Leiden, The Netherlands.
D L
DL
Orsini
Y M
YM
Kooy
M A
MA
Van der Tol
L
L
Struyk
P
P
Van den Elsen
F
F
Koning
D001483:Base Sequence; D015139:Blotting, Southern; D002478:Cells, Cultured; D005802:Genes, MHC Class II; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics; D007376:Interleukin-2 / Q000276:immunology*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology; D013601:T-Lymphocytes / Q000378:metabolism*
D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D016692:Receptors, Antigen, T-Cell, gamma-delta