IL-7 enhances peripheral T cell reconstitution after allogeneic hematopoietic stem cell transplantation
Önder Alpdogan, … , Barry J. Kappel, Marcel R.M. van den Brink
Önder Alpdogan, … , Barry J. Kappel, Marcel R.M. van den Brink
Published October 1, 2003
Citation Information: J Clin Invest. 2003;112(7):1095-1107. https://doi.org/10.1172/JCI17865.
View: Text | PDF
Article Aging

IL-7 enhances peripheral T cell reconstitution after allogeneic hematopoietic stem cell transplantation

Abstract

We used clinically relevant murine allogeneic bone marrow transplantation (BMT) models to study the mechanisms by which IL-7 administration can improve posttransplant peripheral T cell reconstitution. After transplant we could distinguish two populations of mature donor T cells: (a) alloreactive T cells with decreased expression of CD127 (IL-7 receptor α chain) and (b) nonalloreactive T cells, which express CD127 and undergo homeostatic proliferation. IL-7 administration increased the homeostatic proliferation of nonalloreactive T cells, but had no effect on alloreactive T cells and the development of graft-versus-host disease. Allogeneic transplant of purified hematopoietic stem cells and adoptive transfer of thymocytes into lethally irradiated hosts suggested that recent thymic emigrants can undergo homeostatic proliferation and acquire a memory-like phenotype. We found by BrdU pulse-chase, cell cycle, and annexin V analyses that IL-7 administration has significant proliferative and antiapoptotic effects on posttransplant peripheral T cells. We conclude that homeostatic expansion is important for T cell reconstitution after allogeneic BMT and involves both transferred mature T cells and recent thymic emigrants. Apart from its thymopoietic effects, IL-7 promotes peripheral T cell reconstitution through its selective proliferative and antiapoptotic effects on nonalloreactive and de novo–generated T cells, but has no effect on alloreactive T cells.

Authors

Önder Alpdogan, Stephanie J. Muriglan, Jeffrey M. Eng, Lucy M. Willis, Andrew S. Greenberg, Barry J. Kappel, Marcel R.M. van den Brink

×

Figure 2

Options: View larger image (or click on image) Download as PowerPoint
Alloreactive and nonalloreactive donor T cells can be distinguished by t...
Alloreactive and nonalloreactive donor T cells can be distinguished by their phenotype and proliferation kinetics. (a and b) Lethally irradiated (1,300 cGy) C3FeB6F1 (allogeneic, Allo) or B6 (syngeneic, Syn) recipients were transplanted with B6 BM (5 × 106) and CFSE-labeled B6 (Ly5.1+) purified T cells (2 × 107). At various timepoints after BMT, recipients were sacrificed and splenocytes were stained with anti-CD8, -CD25, -CD44, -CD62L, and -CD122 antibodies. Flow cytometric analysis is shown for expression of these antibodies on donor CD8+ T cells 64 hours after BMT (a).CD69 expression on donor CD4 and CD8 T cells in the spleen was determined 16 hours, 40 hours, and 64 hours after BMT (b). (c) Lethally irradiated (750 cGy) B6D2F1/J recipients were transplanted with CFSE-labeled B6 purified T cells (2 × 107). After 64 hours, mice were sacrificed, splenocytes were stained with anti-CD4 and -CD8 antibodies, and FSC intensity was determined. A: nondividing cells; B: slow proliferating cells; C:fast proliferating cells. FSC, forward scatter; % of max, % of maximum number of the cells per group. (d) Lethally irradiated (750 cGy) C3FeB6F1 recipients were transplanted with CFSE-labeled B6 purified T cells (2 × 107). After 64 hours, mice were sacrificed and splenocytes were sorted according to CFSE intensity, shown in a histogram plot as fast- and slow-proliferative cells. Cells were incubated with irradiated C3FeB6F1 splenocytes as stimulators for 5 days. IL-2 (20 IU/ml) was added after 72 hours, and proliferation was determined by 3H-thymidine incorporation.