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Contribution of Naïve and Memory T‐Cell Populations to the Human Alloimmune Response
Author(s) -
Macedo C.,
Orkis E. A.,
Popescu I.,
Elinoff B. D.,
Zeevi A.,
Shapiro R.,
Lakkis F. G.,
Metes D.
Publication year - 2009
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2009.02742.x
Subject(s) - medicine , human memory , immunology , cognition , psychiatry
T‐cell alloimmunity plays a dominant role in allograft rejection. The precise contribution of naïve and memory T cells to this response however remains unclear. To address this question, we established an ex vivo flow‐cytometric assay that simultaneously measures proliferation, precursor frequency and effector molecule (IFNγ, granzyme B/perforin) production of alloreactive T cells. By applying this assay to peripheral blood mononuclear cells from healthy volunteers, we demonstrate that the CD4 + and CD8 + populations mount similar proliferative responses and contain comparable frequencies of alloreactive precursors. Effector molecule expression, however, was significantly higher among CD8 + T cells. Analysis of sorted naïve and memory T cells showed that alloreactive precursors were equally present in both populations. The CD8 + effector and terminally differentiated effector memory subsets contained the highest proportion of granzyme B/perforin after allostimulation, suggesting that these cells present a significant threat to transplanted organs. Finally, we demonstrate that virus‐specific lymphocytes contribute significantly to the alloresponse in certain responder–stimulator HLA combinations, underscoring the importance of T‐cell cross‐reactivity in alloimmunity. These results provide a quantitative assessment of the roles of naïve and memory T‐cell subsets in the normal human alloimmune response and establish a platform for measuring T‐cell alloreactivity pre‐ and posttransplantation.