Significant MLR but not CTL responses against recipient antigens generated in T cells from bone marrow chimeras recovered from acute GVHD

Abstract

BMT is an effective therapy for many otherwise lethal diseases including leukemia. 1 GVHD is one of the most critical complications accompanying BMT. [2][3][4] To reduce the incidence of GVHD, a number of methods have been established in murine and human systems. 4-11 Elimination of mature T cells from donor BM cells (BMC) is one of the most reliable methods. However, the complete elimination of allogeneic T cells has been shown to increase the frequency of failure of allogeneic engraftment. [12][13][14][15][16][17] In addition, it has been reported that GVHD has beneficial effects in preventing recurrence of leukemia via the GVL response. 18 We have reported that BMT mice prepared by inoculation of a small number of T cells with BMC from both MHC class I and non-MHC Ag disparate mice show signs of clinical GVHD at an early stage after BMT. 19 The acute GVHD resulted in abrogation of the thymic negative selection of the self-reactive T cell repertoire. 11,20 In the present study, using the same experimental BMT system we investigated functions and TCR V␤ repertoires of T cells in the bone marrow chimeras which had recovered from the acute GVHD that had been induced by mismatches at the H-2D and non-MHC loci including minor lymphocyte stimulatory (Mls)-1 locus. The Mls-1 a Ag is an endogenous superantigen and stimulates several repertories of T cells in the absence of priming. 21,22 We report here a split tolerance of T cells induced in these chimeras. These T cells showed a significant proliferative response but no CTL activity to the recipient cells. To elucidate the mechanism(s) underlying the split tolerance, we analyzed the pattern of cytokine production by these T cells.

Alloreactivity following in utero transplantation of cytokine-stimulated hematopoietic stem cells

“…In our present model of IUT, enhanced MLR but decreased CTL responses were observed with increased CD4/ CD8 ratios and IL-2 production. The finding that anti-donor MLR, but not CTL responses, increased following transplantation was previously reported [33][34][35] and was related to the expansion of CD4 cells. Similarly, we have observed significant expansion of CD4 cells but not CD8 cells upon reexposure to the donor cells during the postnatal boosts (Fig.…”

The Synthetic Peptide Trp-Lys-Tyr-Met-Val-D-Met Inhibits Human Monocyte-Derived Dendritic Cell Maturation via Formyl Peptide Receptor and Formyl Peptide Receptor-Like 2

“…T cells purified from human PBMCs using nylon wool columns, were used as responders (23), and DCs, which had been treated with vehicle, LPS, WKYMVm plus LPS, or wkymvm plus LPS were used as stimulator cells. A total of 1 ϫ 10 5 allogeneic T cells were added to DCs (1 ϫ 10 4 , 3 ϫ 10 3 , 1 ϫ 10 3 , or 3 ϫ 10 2 ) in 96-well tissue culture plates containing 0.2 ml of medium per well.…”