CMV drives the expansion of highly functional memory T cells expressing NK‐cell receptors in renal transplant recipients. Issue 8 (3rd July 2017)

• Record Type: Journal Article
• Authors: Makwana, Nandini; Foley, Bree; Fernandez, Sonia; Lee, Silvia; Irish, Ashley; Pircher, Hanspeter; Price, Patricia
• Is Part Of: European journal of immunology. Volume 47:Issue 8(2017)
• Page Start: 1324
• Page End: 1334
• Publication Date: 2017-07-03
• Subjects: Cytomegalovirus · NK‐cell receptors · Renal transplantation · T cells; Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201747018
• Languages: English
• ISSNs: 0014-2980

Abstract

Abstract : In RTRs, active and latent CMV infection enhanced T‐cell expression of LIR‐1 and KLRG1 on effector memory and terminally differentiated CD4 and CD8 T cells. Expression of these receptors correlated with increased effector function, i.e. IFNγ production and CD107a expression following stimulation with CMV pp65, CMV IE‐1 or anti‐CD3. Abstract : Cytomegalovirus (CMV) is a common opportunistic infection encountered in renal transplant recipients (RTRs) and may be reactivated without symptoms at any time post‐transplant. We describe how active and latent CMV affect T‐cell subsets in RTRs who are stable on maintenance therapy. T‐cell responses to CMV were assessed in RTRs ( n = 54) >2 years post‐transplant, and healthy controls ( n = 38). Seven RTRs had CMV DNA detectable in plasma. CMV antibody and DNA aligned with increased proportions of CD8 + T cells and reduced CD4/CD8 ratios. This paralleled an expansion of effector memory T‐cell (TEM ), terminally differentiated T‐cell (TEMRA ) and CD57 + TEMRA cell populations. Expression of NK‐cell receptors, LIR‐1 and KLRG1 on CD4 + and CD8 + CD57 + TEM and TEMRA cells correlated with elevated interferon‐γ and cytotoxic responses to anti‐CD3 and increased cytotoxic responses to CMV phosphoprotein (pp) 65 in RTRs who carried CMV DNA. CD8 + T cells from all CMV seropositive RTRs responded efficiently to CMV immediate early (IE) ‐1 peptides. The data show that latent and active CMV infection can alter T‐cell subsets in RTRs many years after transplantation, and up‐regulate T‐cell expression of NK‐cell receptors. This may enhance effector responses of CD4 + and CD8 + T cells against CMV.