Naslov
Follicles in gut-associated lymphoid tissues create preferential survival niches for follicular TH cells escaping T-cell depleting treatment in mice

Autori
Mihalj, Martina ; Kellermayer, Zoltán ; Balogh, Péter

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

Izvornik
Proceedings of The Physiological Society / - , 2012

Skup
Physiology 2012

Mjesto i datum
Edinburgh, Ujedinjeno Kraljevstvo, 02.07.2012. - 05.07.2012

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Peyer’s patches; Thy-1; depletion; follicle; follicular Th cells

Sažetak
INTRODUCTION: Depletion of T cells by monoclonal antibodies is a widely used therapeutic approach for inducing tolerance and preventing graft versus host disease in patients with organ transplants (1). Although a substantial number of CD4 T cells can escape depletion, there are no data on their specific tissue location and phenotypic characteristics in different peripheral lymphoid tissues (2). In the present study we investigated survival, phenotype and location of CD4-positive T cells immediately following anti-Thy-1 monoclonal antibody treatment in mouse. METHODS: BALB/c mice at 6-10 weeks of age were injected i.v. 300 µg of IBL-1 (anti-Thy-1/CD90) monoclonal antibody on two consecutive days and sacrificed 36 hours after first injection. In a separate set of experiments, prior to IBL-1 treatment, mice were immunized by human RBC (100µl/recipient of a 10% suspension in PBS i.p, ) or treated by lymphotoxin beta-receptor fusion protein (100 µg/recipient i.v.), for induction of germinal centre reaction or acute disruption of follicular structure, respectively. For the purpose of evaluating the effect of acute IL-7 withdrawal, mice received simultaneously both anti-Thy-1 (600 µg/recipient) and polyclonal rabbit anti-mouse IL-7 (160 µg/recipient) blocking Abs. Their spleen, lymph nodes and Payers patches (PP) were collected and further processed for the fow cytometric and immunofluorescent microscopic assessment using CD62L, CD44, CD4, CD8, Bcl-2, CXCR5 and PD1 markers. T-cell proliferation was monitored by using BrdU incorporation assay. RESULTS: We found a preferential survival of CD4 T cells in the Peyer's patches and, to a lesser degree, in the mesenteric lymph nodes of BALB/c mice, where majority of the surviving CD4-positive T cells displayed CD44hi/CD62Lneg phenotype corresponding to effector memory T cell features. In addition, these CD4-positive cells also expressed CXCR5 and PD-1 markers characteristic for follicular TH cells (TFH), and were enriched in the Peyer's patch follicles. Using BrdU-incorporation we demonstrate that the immediate survival of these cells does not involve proliferation. Furthermore, simultaneous blockade of IL-7 did not enhance the efficiency of anti-Thy-1 depletion. Induction of germinal center formation during T-dependent immune response in spleen resulted in enhanced survival of splenic TFH cells, while the dissolution of follicular architecture by lymphotoxin beta-receptor antagonist treatment slightly reduced TFH survival. CONCLUSION: Our results thus raise the possibility that the natural germinal center microenvironment in the GALT may be favorable for the survival of T-follicular helper cells of memory phenotype.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA