A CMV-specific γδ T cell clone (4-29) produces TNF in response to tumor epithelial cell lines, but not normal epithelial cell lines.

Latent cytomegalovirus (CMV) infection can reactivate in patients undergoing immunosuppression after organ transplant. But γδ T cells escape immunosuppression and are free to take control of the infection, suggest Halary and colleagues on page 1567. These CMV-reactive γδ T cells also recognized intestinal epithelial tumor cell lines, suggesting that CMV-infected cells and tumor cells may share a common, as yet undefined, γδ T cell antigen.

γδ T cells are a heterogeneous population of T cells that express a restricted T cell receptor repertoire and, unlike conventional αβ T cells, can be activated in a major histocompatibility complex (MHC)-independent fashion by self-antigens. Most subsets of γδ T cells reside in epithelial tissues such as the skin and intestine. Studies in mice have suggested that these cells are required for the control of various viral and bacterial infections, but precise roles for γδ T cells in humans have been difficult to establish.

In previous work, this group noted that a subset of γδ T cells expanded in kidney transplant patients, but only in those with active CMV infections. They now find that γδ T cell lines derived from transplant patients are indeed CMV-specific, as they could kill CMV-infected cells but not cells infected with other related viruses.

In an interesting twist, many of the CMV-reactive γδ T cell lines also recognized epithelial tumor cell lines. Although the identity of the potentially shared ligand remains under investigation, the authors suspect a local stress-induced self-antigen, as CMV replication often occurs preferentially in epithelial cells.

The authors suggest that γδ T cells may be uniquely able to respond to CMV. The virus-specific αβ T cells, which are abundant during primary infections in otherwise healthy individuals, will be crippled by posttransplant immunosuppression. But γδ T cells are not immunosuppressed, and can still attack CMV-infected cells.