| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
*Adult Stem Cell Transplant Program, Department of Medicine, University of Miami Sylvester Cancer Center, Miami, FL 33136;
Transplant Immunology Section, Department of Stem Cell Transplantation and Cellular Therapy; and
The Immunology Program of the University of Texas Health Science Center, Graduate School of Biomedical Sciences, The University of Texas, M. D. Anderson Cancer Center, Houston, TX 77030
Late memory T cell skewing is observed in the setting of immune recovery after cord blood transplantation, and may be associated with inferior control of viral reactivation and cancers. Therefore, we sought to understand how late memory cells differ functionally from earlier stage memory T cells, and whether surface phenotypes associated with differentiation stages were predictably associated with functional signatures. Higher order cytokine flow cytometry allows characterization of human T cells based on complex phenotypic markers and their differential capacity to simultaneously secrete effector proteins, including cytokines and chemokines. We used 8-color, 10-parameter cytokine flow cytometry to characterize the functional activation of human late memory CD8+ T cells defined by CD45RA and CD27 expression (CD27–CD45RA+). We assessed the 15 possible functional signatures of cells defined by production of IL-2, IFN-
, TNF-
, and MIP-1β alone or in combination, following activation with Ags stimulating bypassing surface proteins (PMA:ionomycin) or through the TCR (e.g., viral Ags). Late memory CD8+ T cells produced abundant amounts of CC chemokines (MIP-1β, MIP-1, and RANTES) but not IL-2. IL-2/IFN- coproduction, characteristic of protective immune responses to viral infections, was absent in late memory CD8+ T cells. These data demonstrate that functional cytokine signatures are predictably associated with CD8+ maturation stages, and that the polarization of late memory CD8+ T cells toward CC chemokine production and away from IL-2 production suggests a unique functional role for this subset.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by Grants R01 CA109326 and R01 HL091749 from the National Institutes of Health (to K.V.K.) and by Grant 6178-06 from the Leukemia and Lymphoma Society Translational Research Program (to K.V.K.).
T.K.K. performed the primary work and wrote the manuscript. L.S.J. made critical contributions to the development of methodologies. E.D.W. assisted with flow cytometric analysis and reviewed the data. J.K. assisted with analysis of data. Q.M. provided mentorship and helped analyze the data. K.V.K. conceived the project, supervised the laboratory work, analyzed the data, and cowrote the manuscript.
2 Address correspondence and reprint requests to Dr. Krishna V. Komanduri, Adult Stem Cell Transplant Program, Division of Hematology-Oncology, Department of Medicine, Sylvester Cancer Center, Mail Code D8-4, University of Miami, 1121 NW 14th Street, Room 311, Miami, FL 33136. E-mail address: kkomanduri{at}med.miami.edu
3 Abbreviations used in this paper: DC, dendritic cell; CFC, cytokine flow cytometry; SEB, staphylococcal enterotoxin B.
4 The online version of this article contains supplemental material.
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
