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Deleting LAG-3 Accelerates Cardiac Allograft Rejection and Augments T Cell Memory in Mice.

J. Erfe,1,2 C. Yang,1 D. Ndishabandi,1 I. Rosales,1 R. White,1 P. Russell,1 R. Colvin,1 J. Madsen,1 A. Alessandrini.1

1Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA
2Yale School of Medicine, New Haven, CT

Meeting: 2017 American Transplant Congress

Abstract number: B7

Keywords: Graft survival, Heart, knockout, Mice, T cells

Session Information

Session Name: Poster Session B: Acute and Chronic Rejection

Session Type: Poster Session

Date: Sunday, April 30, 2017

Session Time: 6:00pm-7:00pm

 Presentation Time: 6:00pm-7:00pm

Location: Hall D1

Purpose: Lymphocyte Activation Gene-3 (LAG-3) expresses a transmembrane receptor on activated immune cells such as T cells, NK cells, and plasmacytoid dendritic cells. It is involved in effector and regulatory functions. Here we examine the effects of blocking the LAG-3 pathway on cardiac allograft rejection.

Methods: DBA/2 donors (H2-d) cardiac allografts were transplanted without immunosuppression into C57BL/6 wild-type (WT) controls, LAG-3-/- (KO) on a C57BL/6 background, and C57BL/6 treated with LAG-3 neutralizing antibody. Memory T-cell secretion of IFN-g to DBA/2 antigens was assessed via ELISPOT.

Results: Allografts in WT recipients rejected on average in 8.1 days. Allografts in LAG-3-/- KO recipients rejected on average in 6.3 days (p=0.03*). Antibody-treated recipients rejected on average in 7.0 days (p=0.27). IFN-g secretion by LAG-3-/- KO splenic T cells was on average 2.6-fold higher than WT T cells across all time points (p=0.005**, Table 1). Rejected allografts in LAG-3-/- KO recipients showed focused endothelial lymphocytic infiltration that was magnified at 1 week post-rejection (Figure 1).

Table 1. Antigen-Specific Increased Memory T-Cell IFN-g Response

KO/WT Ratio Mann-Whitney U Test (KO vs. WT)
1-3 Days 2.7 P=0.05*
1 Week 1.6 P=0.10
4 Weeks 2.8 P=0.05*
Total 2.4 P=0.005**

*5% level significance

**1% level significance

Figure 1. H&E Comparison of WT and KO GraftsAt 1 week post-rejection, WT recipients show diffuse intercellular infiltration with patent vessels (A) while LAG-3-/- KO recipients show lymphocytic infiltration of endothelium and vascular collapse (white arrow) (B). H&E, 40x.

Conclusions: The absence of LAG-3 leads to slightly faster allograft rejection, with an increase in the T-cell memory response to donor antigen. These findings suggest that maintenance of surface LAG-3 protects H-2 mismatched cardiac allografts and could be an important target for immunosuppressive therapy.

CITATION INFORMATION: Erfe J, Yang C, Ndishabandi D, Rosales I, White R, Russell P, Colvin R, Madsen J, Alessandrini A. Deleting LAG-3 Accelerates Cardiac Allograft Rejection and Augments T Cell Memory in Mice. Am J Transplant. 2017;17 (suppl 3).

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To cite this abstract in AMA style:

Erfe J, Yang C, Ndishabandi D, Rosales I, White R, Russell P, Colvin R, Madsen J, Alessandrini A. Deleting LAG-3 Accelerates Cardiac Allograft Rejection and Augments T Cell Memory in Mice. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/deleting-lag-3-accelerates-cardiac-allograft-rejection-and-augments-t-cell-memory-in-mice/. Accessed June 5, 2025.

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