V delta 1 T cells expanded in the blood throughout HIV infection display a cytotoxic activity and are primed for TNF-alpha and IFN-gamma production but are not selected in lymph nodes.
We have previously reported significant alterations of gamma delta subset distribution in the peripheral blood of HIV-infected donors. These modifications are characterized by the depletion of the V delta 2 subset associated with a strong increase in peripheral V delta 1 T cells. In addition, the latter exhibit ex vivo an activated phenotype and show a restricted complementarity-determining region 3 (CDR3) repertoire. In the present report we first address the question of the origin of these expanded cells. The lack of expansion and the Gaussian complementarity-determining region 3 size distribution of lymph node V delta 1 T cells suggest that lymph nodes do not represent the site of specific activation of this subset. The function of blood V delta 1 T cells was also explored. We report that patients' V delta 1 T cells express high levels of perforin and display an in vitro cytotoxic activity, whose characteristics are different from those of NK and LAK cells. In addition, single cell analysis of cytokine production revealed that, in contrast to V delta 1 T cells from control donors, patients' V delta 1 T cells are primed in vivo for IFN-gamma and TNF-alpha production. Together, these results indicate that in the course of HIV infection, expanded blood V delta 1 T cells are differentiated into a functional subset and raise the question of the contribution of this subset to AIDS pathogenesis.
Boullier
S
S
Unité d'Oncologie Virale, Département SIDA et Rétrovirus, Institut Pasteur, Paris, France.
Dadaglio
G
G
Lafeuillade
A
A
Debord
T
T
Gougeon
M L
ML
D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D017637:Clonal Deletion; D003602:Cytotoxicity, Immunologic; D015658:HIV Infections / Q000097:blood / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis*; D008198:Lymph Nodes / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis / Q000097:blood*; D013602:T-Lymphocytes, Cytotoxic / Q000145:classification / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D016692:Receptors, Antigen, T-Cell, gamma-delta; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma