Selective outgrowth of CD45RO+ V gamma 9+/V delta 2+ T-cell receptor gamma/delta T cells early after bone marrow transplantation

Before and after bone marrow transplantation (BMT) for hematologic malignancies, peripheral blood mononuclear cells from 10 patients were obtained. The relative and absolute numbers of CD3+ T-cell receptor yS+ (TCRyS+) cells, as defined by the reaction of monoclonal antibodies (MoAbs) directed against CD3 and the TCR yS (anti-TCRyS-1). were determined. Before transplantation, eight of nine patients tested had less than 10% CD3+TCRyS+ cells. Consistent increased numbers of yS cells up to eightfold the pretransplant level can be seen in four of nine patients tested within the first 4 months after BMT. The large majority of early posttransplant yS and 4 T cells express the CD45RO antigen, which is usually expressed on "memory" cells only. The V-region usage of the TCRyS' T cells was analyzed using fresh mononuclear cells and MoAbs against known Vy and V6 regions. For more detailed analysis, CD3'TCRyS + cells were WO DISTINCT FORMS of the T-cell receptor (TCR) T have been described, the UP TCR and the y8 TCR.'32 The y8 TCR is expressed by a minority of CD3+ cells (0.5% to 17%) in peripheral blood (PB) and thymus.',3 The y8 cells form a distinct and functionally heterogeneous T-cell lineage and are evenly distributed throughout the lymphoid ~ystem.~ Monoclonal antibodies (MoAbs) specific for the human y8 TCR as well as for V-regions have been described?-" Although the function of TCRy8 cells remains largely unknown, recent reports indicate that these cells are capable of interacting with a heterogeneous set of ligands, among which are alloantigenic determinants, tetanus toxoid, mycobacterial (heat shock) proteins,''~'Z and Staphylococcal enterotoxin A (SEA).I3 Studies in the mouse have indicated that the y8 TCR is expressed before the aP TCR during thymic ontogeny. Populations of y8 TCR' cells are intermittently generated that express characteristic TCRS.'~,'' These waves appear to home specifically to certain epithelia in the skin and in the gut.I6 It has already been shown that rearrangements involving Cy1 precede those involving Cy2, and recent results indicate that, during early fetal ontogeny, rearrangements involving the Cy1 constant region occur before those involving the Cy2 constant region gene ~egment.'~"~ Also, early in human fetal development a wave of TCRy8 cells exists that preferentially uses the V82 gene segment." The kinetics of engraftment after bone marrow transplantation (BMT) may serve as a model system to study the TCRy8 repopulation. After BMT, relative and absolute increased numbers of TCRyG cells have been reported, suggesting differences in repopulation rates between TCRaP and TCRy8 cells after