Naslov
Preferential survival of follicular T helper cells in gut-associated lymphoid tissues following T-cell depleting treatment

Autori
Mihalj, Martina ; Balogh, Péter

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

Izvornik
Immunologiai Szemle / Szekanecz, Zoltan - , 2011

Skup
40th Annual Meetinh of the Hungarian Society for Immunology

Mjesto i datum
Kecskemét, Mađarska, 12.10.2011. - 14.10.2011

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Međunarodna recenzija

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

Sažetak
Introduction: In our recent studies on the early effects of experimental T-cell depletion we have demonstrated that among peripheral lymphoid organs lymph nodes (pLN) present with the highest capacity for rescuing CD4 T cells. Consistent with previous reports we found the preference of memory T cell amongst the T cells resisting treatment. In the present study we investigated T-cell survival in Peyer’s patches (PPs) and mesenteric lymph nodes (mLNs) as organized gut-associated lymphoid tissues. Materials and Methods: BALB/c mice at 6-10 months of age were injected i.v. 300 µg of IBL-1 (anti-Thy-1/CD90) monoclonal antibody (mAb) on two consecutive days, and sacrificed 36 hours after the first injection. To assess depletion kinetics and IBL-1 penetration into the tissue some mice were sacrificed after 0.5, 1, 2, 4, 8 or 24 hours. Their spleen, pLN, mLNs and PPs were collected and further processed for the flow cytometric and immunofluorescent microscopic assessment using CD62L, CD44, CD3, CD4, CD8, B220, Bcl-2, CXCR5 and PD1 markers. T-cell proliferation was monitored by using BrdU incorporation assay. Results: Application of over saturating amount of IBL-1 mAb was proved by high level of residual IBL-1 activity in the sera. IBL-1 tissue penetration showed similar kinetics, achieving the highest level of T-cell saturation already after 2 hours but was 10 fold higher in spleen than in the pLNs. CXCR5/PD-1 positive CD4 T cells were significantly enriched in mLN and were the majority of surviving cells in PPs upon treatment. A substantial fraction of the surviving CD4 T cells were located in the follicles within PPs. In addition, the CXCR5 positive CD4 T cells displayed CD44hi/CD62Lneg phenotype characteristic for effector memory T cells. There was no significant change in Bcl-2 protein expression among surviving CD4 T-cells, and analysis of BrdU incorporation showed no substantial proliferation among CD4 T-cells that would indicate active homeostatic proliferation. Conclusions: The absence of any measurable CD4 proliferation confirms the relative resistance of TFh cells, without the need for upregulating Bcl-2 protein level. The protective capacity of PP and mLN are similar to that we have previously demonstrated in pLN. Our results thus raise the possibility that the germinal center microenvironment in the gut-associated lymphoid tissues may be favorable for the survival of T-follicular helper cells of memory phenotype.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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