High‐Quality CMV‐Specific CD4+ Memory Is Enriched in the Lung Allograft and Is Associated With Mucosal Viral Control

• Published in: American journal of transplantation Vol. 13; no. 1; pp. 146 - 156
• Main Authors: Akulian, J. A., Pipeling, M. R., John, E. R., Orens, J. B., Lechtzin, N., McDyer, J. F.
• Format: Journal Article
• Language: English
• Published: Hoboken, NJ Wiley 01-01-2013; Elsevier Limited
• Subjects: Adult; Alveoli; Biological and medical sciences; Bronchoalveolar Lavage Fluid; Bronchus; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Chronic infection; CMV; Cytomegalovirus; Cytomegalovirus - immunology; Cytomegalovirus Infections - immunology; Data processing; Female; Flow Cytometry; gamma -Interferon; Humans; Immunity, Mucosal; Immunologic Memory; Immunological memory; Infections; Infectious diseases; Interferon-gamma - immunology; Interleukin 2; Leukocytes (mononuclear); Lung; lung transplant; Lung Transplantation - immunology; Lungs; Lymphocytes T; Macrophage inflammatory protein; Male; Medical sciences; memory; Memory cells; Middle Aged; Mortality; Mucosal immunity; Peripheral blood mononuclear cells; Phosphoproteins; pp65 protein; Prospective Studies; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; T cells; Transplants & implants; Tumor necrosis factor- alpha; viral control; Viral diseases; lung transplant; Mucosa; Memory; Lung; Check; Transplantation; Homotransplantation; T cells; Respiratory system; Betaherpesvirinae; Human cytomegalovirus; Association; Surgery; Quality; T-Lymphocyte; Graft; High; Opportunistic infection; Herpesviridae; CMV; viral control; Infection; Virus; Treatment; Surveillance; Viral disease
• ISSN: 1600-6135; 1600-6143
• DOI: 10.1111/j.1600-6143.2012.04282.x

The maintenance of CMV‐specific T cell memory in lung transplant recipients (LTRs) is critical for host defense and allograft durability, particularly in donor+/recipient− (D+R−) individuals who demonstrate increased mortality. We studied CD4+ and CD8+ CMV‐specific memory responses to phosphoprotein 65 (pp65) in a prospective cohort of 18 D+R− LTRs, from bronchoalveolar lavage (BAL)‐obtained lung mononuclear cells (LMNC) and PBMC. Unexpectedly, pp65‐specific CD4+ and CD8+ IFN‐γ memory responses from LMNC were similar, in contrast to persistent CD8+ predominance in PBMC. Unlike the pulmonary CD8+ predominance during acute primary infection, compartmental equalization occurred in the CMV‐specific CD8+ memory pool during chronic infection, whereas CMV‐specific CD4+ memory was enriched in the bronchoalveolar space. Moreover, CMV‐specific CD4+ memory T cells with multifunctional production of IFN‐γ, TNF‐α, IL‐2 and MIP‐1β were significantly increased in LMNCs, in contrast to similar intercompartmental CD8+ memory function. Moreover, the absolute number of CMV‐specific CD4+IFN‐γ+ memory cells in BAL was significantly increased in LTRs exhibiting viral control compared to those with CMV early antigen positivity. Collectively, these data demonstrate both preferential distribution and functional quality of CMV‐specific CD4+ memory in the lung allograft during chronic infection, and show an important association with CMV mucosal immunity and viral control.
This study shows that cytomegalovirus‐specific CD4+ memory T cells are enriched in the lung allograft, multifunctional, and associated with mucosal viral control in lung transplant recipients.