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Naïve subset develops the most important alloreactive response among human CD 4 + T lymphocytes in Human Leukocyte Antigen‐identical related setting
Author(s) -
Chérel Mathilde,
Choufi Bachra,
Trauet Jacques,
Cracco Pascale,
Dessaint JeanPaul,
YakoubAgha Ibrahim,
Labalette Myriam
Publication year - 2014
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/ejh.12283
Subject(s) - immunology , c c chemokine receptor type 7 , t cell , antigen , biology , cytotoxic t cell , memory t cell , cd8 , in vitro , immune system , chemokine , genetics , chemokine receptor
In longitudinal clinical studies, receiving a high percentage of allogeneic donor‐derived CD 4 + CCR 7 + T cells, which include naïve and central memory subsets have been correlated with increased incidence and severity of acute GVHD . Whether naïve and central memory CD 4 + T‐cell subsets contribute more or equally to alloimmune responses are still unclear in human. The aim of this study was to investigate in vitro the alloreactive response of purified naïve, central memory, and effector memory CD 4 + T‐cell subsets in HLA identical setting. By coculturing monocyte‐derived dendritic cells and purified CD 4 + T‐cell subsets, from healthy HLA ‐identical male and female sibling pairs, we found that naïve CD 4 + CCR 7 + CD 45 RA + T cells developed the highest proliferative response upon stimulation by minor histocompatibility antigens and were progressively driven to produce high levels of interferon‐γ, tumor necrosis factor, and interleukin‐6. Comparatively, the central memory CD 4 + CCR 7 + CD 45 RA neg subset proliferated to a lower extent and produced very low amounts of pro‐inflammatory cytokines while the CCR 7 neg effector memory CD 4 + subset was unresponsive. This study demonstrates the superior capacity of naïve CD 4 + T cells to mount a primary alloreactive response as compared to central memory T cells. Their proliferative response associated with a pro‐inflammatory differentiation makes them potentially acute GVHD inducers. These in vitro results in line with what we have observed in clinical studies and may also lend support to approaches of partial selective T‐cell depletion for GVHD prevention.