Session Time: 5:30pm-6:30pm
Presentation Time: 5:30pm-6:30pm
Location: Exhibit Hall E
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.
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).
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+.
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 March 26, 2019.
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