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. 2010 Jan;21(1):181-8.
doi: 10.1681/ASN.2008101072. Epub 2009 Aug 27.

Cytomegalovirus-induced gammadelta T cells associate with reduced cancer risk after kidney transplantation

Lionel Couzi  1 , Yann Levaillant, Abdellah Jamai, Vincent Pitard, Regis Lassalle, Karin Martin, Isabelle Garrigue, Omar Hawchar, François Siberchicot, Nicholas Moore, Jean-François Moreau, Julie Dechanet-Merville, Pierre Merville
Affiliations

Cytomegalovirus-induced gammadelta T cells associate with reduced cancer risk after kidney transplantation

Lionel Couzi et al. J Am Soc Nephrol. 2010 Jan.

Abstract

An increase in the number of blood gammadelta T cells follows cytomegalovirus (CMV) infection in kidney transplant recipients. These cells react against CMV-infected cells and tumor epithelial cells in vitro. We hypothesized that these CMV-induced gammadelta T cells play a protective role against cancer in kidney transplant recipients. We performed a longitudinal case-control study involving 18 recipients who developed cancer between 2 and 6 yr after transplantation and 45 recipients who did not. The median percentage of gammadelta T cells among total lymphocytes in patients with malignancies was significantly lower compared with that in control patients at 6, 12, and 18 mo before the diagnosis of cancer. Patients with a gammadelta T cell percentage of more than 4% were protected from cancer. An increase of the Vdelta2(neg) gammadelta T cell subset significantly associated with lower incidence of cancer only in recipients who experienced pre- or postgraft CMV infection. Finally, a retrospective follow-up of 131 recipients for 8 yr revealed that CMV-naive recipients had an approximately 5-fold higher risk of cancer compared with CMV-exposed patients. In summary, these results suggest a protective role of CMV exposure against cancer in kidney transplant recipients.

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Figures

Figure 1.
Figure 1.
Evolution of γδ T cells. Evolution of the median (A) number of lymphocytes, (B) percentage of γδ T cells, (C) Vδ2neg γδ T cells, and (D) Vδ2pos γδ T cells among total T cells before and after cancer occurrence in KTRs with cancer (♦) and their matched controls (□). (E, F) Evolution of the medians of Vδ2neg γδ T cell percentage before and after cancer occurrence in KTRs with cancer (♦) and their matched controls (□) according to history of CMV. (E) Patients who have been in contact with CMV (before or after transplantation). (F) Patients naïve for CMV infection.
Figure 2.
Figure 2.
Cumulative survival without cancer development in KTRs stratified according to history of CMV infection (pre- or postgraft CMV infection). Kaplan–Meier analysis was used. Comparison was made using the log-rank test.
Figure 3.
Figure 3.
In vitro antitumor reactivity of CMV-induced Vδ2neg γδ T cells. γδ T cells from either patients who developed CMV-infection and did not display cancer (CMV+ cancer-free) or patients who did not develop any CMV infection but displayed a cancer (CMV-free cancer+) were sorted from PBMCs. γδ T cells were then expanded in culture RPMI medium supplemented with 10% human serum, 1000 U/ml rIL-2, 15 ng/ml rIL-15, and irradiated autologous PBMCs. After 1 mo, those γδ T cell lines were incubated with the A431 (epidermoid carcinoma) and the Daudi (Burkitt's lymphoma) cell lines for 24 h in the presence of rIL-12 and rInterferon-α. IFN-γ released into the supernatant was quantified by ELISA.
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