Human CD62L– memory T cells are less responsive to alloantigen stimulation than CD62L+ naive T cells: potential for adoptive immunotherapy and allodepletion

A high proportion of donor CD4+ T cells expressing the lymph node-homing chemokine receptor CCR7 increases incidence and severity of acute graft-versus-host disease in patients undergoing allogeneic stem cell transplantation for hematological malignancy

“…This finding is consistent with results reported on the overlapping population of CD4 þ CD62L þ T cells. 16 In the current study, acute GVHD was correlated to cells expressing CCR7 only within the CD4 þ population. This is consistent with two recent reports.…”

“…In vitro, no difference was found between alloresponses of fractionated CD8 þ CD62L þ and CD8 þ CD62L neg subsets, which were even lower than those of the poor responsive CD4 þ CD62L neg human subset. 16 In vivo, tracking donor cells during acute GVHD in mice has demonstrated that proliferation of CD4 þ T cells preceded that of CD8 þ T cells in murine lymphoid organs. 2 The importance of this subset in initiating acute GVHD is presumably linked to the necessary help that CD4 þ T cells provide to the generation of long-term CD8 þ responses.…”

“…The strong association evidenced between the percentage of CD4 þ CCR7 þ T cells infused and the development and severity of acute GVHD might reflect the predominant distribution of alloreactive T cells in the naive and central memory subsets, as described in experimental models for naive and central memory subsets. 13,16,33 In vitro alloresponses could not be tested in our patients, but we performed one-way mixed leukocyte cultures to compare healthy control subjects with a low or a high percentage of CD4 þ CCR7 þ T cells. In vitro alloresponses were consistently higher when responder PBMCs contained more CD4 þ CCR7 þ T cells.…”

“…13,14 Transfer of CD62L þ T CM cells could also prevent the initiation of transplantation tolerance. 15 In humans, it has been shown that CD4 þ CD62L þ T cells responded better to alloantigens than the CD62L neg memory subsets in both proliferation and cytotoxicity assays, 16 and in vitro-generated T CM appeared to be more potent than T EM in an experimental model of GVHD. 17 Thus, the initiation of GVHD seems to depend on the representation of alloreactive cells within naive and/or central memory subsets in the graft, but no clinical study has yet sustained these experimental or in vitro data.…”

Depletion of naive T cells using clinical grade magnetic CD45RA beads: a new approach for GVHD prophylaxis

“…[4][5][6] We have also described that flow cytometry-sorted CD45RA-negative (CD45RA À ) T cells are enriched for memory cells and mediate significantly reduced alloreactive in vitro functions versus CD45RA-positive (CD45RA þ ) T cells of the same donor. 6 In the current work, we established the immunomagnetic depletion of CD45RA þ cells from entire LPs under good manufacturing practice conditions and analyzed pre-and post-depletion products for cell composition as well as for T-cell responses to pathogens and allogeneic cells.…”