Human CMV-Specific CD8 T Cells Exhibit Distinct Phenotypes and Distribution Patterns in Tissues and Circulation
1Columbia Center for Translational Immunology, Columbia University Medical Center, New York
2Medicine, Columbia University Medical Center, New York
3Microbiology and Immunology, Columbia University Medical Center, New York
4Surgery, Columbia University Medical Center, New York
5University of Melborne, Melbourne, Australia.
Meeting: 2015 American Transplant Congress
Abstract number: D245
Keywords: Cytomeglovirus
Session Information
Session Name: Poster Session D: Viral Infections
Session Type: Poster Session
Date: Tuesday, May 5, 2015
Session Time: 5:30pm-6:30pm
Presentation Time: 5:30pm-6:30pm
Location: Exhibit Hall E
Introduction
CMV persists and is controlled by T cells in multiple tissues; however, study of CMV responses has largely been limited to blood containing only 2-3% of T cells. To gain new insights we evaluated the frequency, distribution and function of CMV-specific CD8 T cells in blood, lymphoid and mucosal tissues.
Methods
Blood, bone marrow (BM), spleen, iliac, mesenteric and lung lymph nodes (LN) and mucosal tissues (lung, colon) were obtained from 10 CMV+ donors aged 23-57. CMV-specific T cells were analyzed using MHCI multimers, and phenotypic markers corresponding to naïve, memory and effector subsets, activation and maintenance (CD28, CD127 [IL7 receptor]), and tissue residence (CD69, CD103).
Results
In all individuals CMV-specific T cells were identified at significant frequencies (2-18%) in blood, BM, spleen, lung, and LNs, with low or negligible frequencies in intestines. However, distribution and subset delineation of CMV-specific T cells followed one of two distinct patterns. In 6/10 individuals there was a biased high frequency of CMV-specific T cells in circulation, including blood, BM and lung, which were predominantly of an activated (CD28-) terminally differentiated TEMRA or TEM phenotype. In the remaining 4/10 individuals, high frequencies of CMV-specific T cells were found in LNs, and exhibited a naïve-like phenotype (CCR7+ CD45RA+ CD28+ CD27+ CD127+ CD95-), and when activated rapidly downregulated CCR7 expression adopting a TEMRA phenotype. Naïve-like CMV-specific T cells were only 12-34% CD69+ compared to CMV-specific EM (35-88%) and EMRA (23-78%) outside of blood. CMV-specific T cells in colon were CD103+.
Conclusion
CMV-specific CD8 T cell immunity is focused in different tissues which varies between donors, with some donors having lymphoid-focused circulating responses of a unique naïve-like phenotype which may represent a resting EMRA population, and others with CMV-specific EMRA and/or EM subsets in circulation with a proportion exhibiting features of tissue resident T cells. Whether these different populations reflect state of viral latency or persistence is being investigated.
NIH AI106697, S10RR027050-01A1, UL1 TR000040
To cite this abstract in AMA style:
Gordon C, Thome J, Tomer G, Farber D. Human CMV-Specific CD8 T Cells Exhibit Distinct Phenotypes and Distribution Patterns in Tissues and Circulation [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/human-cmv-specific-cd8-t-cells-exhibit-distinct-phenotypes-and-distribution-patterns-in-tissues-and-circulation/. Accessed November 21, 2024.« Back to 2015 American Transplant Congress