Naslov
Tissue location as a determinant of T-cell survival following in vivo T-cell depleting treatment

Autori
Mihalj, Martina ; Balogh, Peter

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Immunology quarterly / Szegedi, G - Budimpešta, 2010, 16-17

Skup
A Magyar Immunologiai Tarsasag XXXIX. Vandorgyulese

Mjesto i datum
Szeged, Mađarska, 03.11.2010. - 05.11.2010

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Domaća recenzija

Ključne riječi
secondary lymphoid organs; homeostatic proliferation; monoclonal antibody mediated T-cell depletion; memory T cell

Sažetak
Introduction: T cell depletion is a widely used therapeutic approach in transplanted patients to suppress rejection. These therapeutic antibodies never reach complete T cell elimination. Several studies with mice and humans showed that T cells with memory-like phenotype are relatively resistant to antibody-mediated T-cell depletion. In the absence of data on the possible survival niches in the peripheral lymphoid tissues, we investigated where the resistant cells are spared from depletion during the early phase of treatment. Materials and Methods: We used IBL-1 rat monoclonal antibody against Thy-1/CD90 antigen in wild-type (BALB/c and [B6xBALB/c] F1) and transgenic mouse strains (c3-/-, AND TcR Tg). The depletion efficiency was monitored by the flow cytometric and immunofluorescent microscopic assessment of peripheral lymphoid tissues using CD62L, CD44, CD4, CD8, Foxp3 and PD1 markers. In vitro T-cell activation was monitored using Ca-assay and phosphotyrosine (PY) immunoblots. Results: In F1 mice in the blood and the spleen T-cells were almost completely eliminated, while in the peripheral lymph node (pLN) one third of the T-cells survived. In pLN samples we found significant (p=0, 009) increase of central memory (CD62L+/CD44hi) T cells. In AND mice with a large increase in memory T cells, 24 to 36 hours after the application of IBL-1 mAb we did not find any T-cell depletion in pLN’s compared to the spleen and blood. In contrast to F1 mice, both central and effector memory (CD62L-/CD44hi) T cells showed significant reduction. In BALB/c mice an extensive drop of naïve T-cell frequency and enrichment of memory cell type was observed in all tissue samples. However, even in BALB/c mice pLN T cells showed significant resistance when compared with blood and spleen. In mice lacking complement factor C3 the degree of lymphocyte depletion was the same as in wild-type BALB/c mice. Immunoflorescence on tissue sections did not reveal any alteration of specific regional tissue location of survival T-cells Also, we found no difference in the frequency of regulatory T cells (CD4+/Foxp3+) upon anti-Thy-1 treatment. In vitro exposure to IBL-1 mAb induced a low but immediate calcium influx. Preliminary Western blot analyses by anti-PY mAb in lymphocyte lysate from anti-Thy-1 mAb-treated animals did not reveal any increase in phosphotyrosine content. Conclusions: Our results showed that pLNs in mice provide a protective environment for T-cell upon treatment with depleting antibodies, irrespectively of mouse strain, but with various capacities for protection. As there are no parallel data in humans, such studies in experimental animals are likely to lend new data on the course of lymphocyte depletion and survival.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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