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Breast Milk-Derived Antigen-Specific CD8⁺ T Cells: An Extralymphoid Effector Memory Cell Population in Humans¹

Steffanie Sabbaj^2,*, Mrinal K. Ghosh^2,, Bradley H. Edwards, Ruth Leeth, W. Don Decker, Paul A. Goepfert^*, and Grace M. Aldrovandi^3,,,

Departments of ^* Medicine, Microbiology, and Pediatrics, University of Alabama, Birmingham, AL 35294; and Department of Infectious Diseases, Children’s Hospital Los Angeles, Los Angeles, CA 90027

Although mouse studies have demonstrated the presence of an effector memory population in nonlymphoid tissues, the phenotype of human CD8⁺ T cells present in such compartments has not been characterized. Because of the relatively large number of CD8⁺ T cells present in breast milk, we were able to characterize the phenotype of this cell population in HIV-infected and uninfected lactating women. CMV, influenza virus, EBV, and HIV-specific CD8⁺ T cells as measured by the IFN- ELISPOT and MHC class I tetramer staining were all present at greater frequencies in breast milk as compared with blood. Furthermore, a greater percentage of the breast milk CD8⁺ T cells expressed the intestinal homing receptor, CD103, and the mucosal homing receptor CCR9. Breast milk T cells were predominantly CD45RO⁺HLADR⁺ and expressed low levels of CD45RA, CD62L, and CCR7 consistent with an effector memory population. Conversely, T cells derived from blood were mainly characterized as central memory cells (CCR7⁺CD62L⁺). These results demonstrate a population of extralymphoid CD8⁺ T cells with an effector memory phenotype in humans, which could contribute to enhanced local virologic control and the relative lack of HIV transmission via this route.