Expansion of mycobacterium-reactive γδ T cells by a subset of memory helper T cells

Human γδ T cells expressing the Vγ9/Vδ2 T-cell receptor have been previously found to proliferate in response to certain microorganisms and to expand throughout life, presumably because of extrathymic activation by foreign antigens. In vitro expansion of Vγ9/Vδ2 cells by mycobacteria has been previously shown to be dependent on accessory cells. In order to gain an insight into the mechanisms involved in the expansion of these cells, we have undertaken to identify the peripheral blood subset of cells on which proliferation of Vγ9/Vδ2 cells in response to mycobacteria is dependent. Contrary to their role in antigen presentation to αβ T cells, professional antigen-presenting cells, such as monocytes, B cells, and dendritic cells, were unable to provide the cellular support for the expansion of Vγ9/Vδ2 cells. Selective depletion of T-cell subsets, as well as the use of highly purified T-cell populations, indicated that the only subset of peripheral blood cells that could expand Vγ9/Vδ2 cells were CD4⁺ CD45RO⁺ CD7^- αβ T cells. These cells underwent distinct intracellular signaling events after stimulation with the mycobacterial antigen. Expansion of Vγ9/Vδ2 cells by αβ T cells was dependent on cell-cell contact. This is the first evidence that a small subset of the memory helper T-cell population is exclusively responsible for the peripheral expansion of Vγ9/Vδ2 cells. These data illustrate a unique aspect of antigen recognition by γδ T cells and provide new means to study their immune defense role.