L-selectin-dependent lymphoid occupancy is required to induce alloantigen-specific tolerance.

TitleL-selectin-dependent lymphoid occupancy is required to induce alloantigen-specific tolerance.
Publication TypeJournal Article
Year of Publication2002
AuthorsBai Y, Liu J, Wang Y, Honig S, Qin L, Boros P, Bromberg JS
JournalJ Immunol
Volume168
Issue4
Pagination1579-89
Date Published2002 Feb 15
ISSN0022-1767
KeywordsAnimals, Antibodies, Monoclonal, Cell Movement, Cells, Cultured, Fingolimod Hydrochloride, Graft Survival, Heart Transplantation, Immunosuppressive Agents, Isoantigens, Kinetics, L-Selectin, Lymph Nodes, Lymphocyte Activation, Lymphoid Tissue, Mice, Mice, Knockout, Propylene Glycols, Sphingosine, Spleen, T-Lymphocytes, Transplantation Tolerance
Abstract

Maneuvers that interfere with signals 1, 2, 3, or Ag processing can result in indefinite allograft survival. However, they are not applicable to all tissues, strains, or species, suggesting that there are additional levels of immune regulation. We hypothesized that secondary lymphoid organs are important for interactions among lymphocytes, alloantigen, and immunosuppressants that lead to tolerance. To explore this, cardiac allografts were performed with a tolerogenic immunosuppressive regimen. Concurrent administration of anti-L-selectin (CD62L) Ab, which prevents lymph node homing, prevents indefinite allograft survival and tolerance. Anti-CD62L Ab is not costimulatory, and Fab and F(ab')(2) anti-CD62L have similar activities. Flow cytometry and histologic examination show that Ab shifts T cells away from lymph nodes and into spleen, peripheral blood, and graft. Tolerance is not induced in CD62L(-/-) mice, and adoptive transfer of CD62L(-/-), but not CD62L(+/+), T cells prevents tolerization in wild-type recipients. FTY720, an immunosuppressant that promotes chemokine-dependent, but CD62L-independent, lymph node homing, reverses the Ab effect. Blockade of other homing receptors also prevents tolerization. These results indicate that T lymphocytes use CD62L-dependent migration for alloantigen-specific tolerance, and suggest that lymph nodes or other lymphoid tissues are an important site for peripheral tolerization to alloantigen.

DOI10.4049/jimmunol.168.4.1579
Alternate JournalJ Immunol
PubMed ID11823485
Grant ListR01 AI41428 / AI / NIAID NIH HHS / United States
Related Faculty: 
Lihui Qin, M.D., Ph.D.

Pathology & Laboratory Medicine 1300 York Avenue New York, NY 10065 Phone: (212) 746-6464
Surgical Pathology: (212) 746-2700