Naslov
Monoklonskim protutijelima posredovana modulacija limfocitne homeostaze
(Monoclonal antibody-mediated modulation of lymphocyte homeostasis)

Autori
Martina Mihalj

Vrsta, podvrsta i kategorija rada
Ocjenski radovi, doktorska disertacija

Fakultet
Medicinski fakultet

Mjesto
Osijek

Datum
20.02

Godina
2013

Stranica
101

Mentor
Balogh, Peter ; Drenjancevic, Ines

Ključne riječi
Thy-1; depletion; follicular TH cells; Peyer's patches; follicle

Sažetak
Purpose: Although a substantial number of T cells may escape depletion by monoclonal antibody treatment in vivo in patients undergoing immunosuppression, their specific tissue location and phenotypic characteristics in different peripheral lymphoid tissues have not been analyzed in details. In the present study, we investigated the survival of CD4-positive T cells immediately following anti-Thy-1 monoclonal antibody treatment in mouse. Methods: We used multiparameter flow cytometry for cell surface and intracellular markers as well as BrdU assay for lymphocyte subset and cell cycle analysis, and immunofluorescence with morphometric measurement for tissue positioning. Results: We found a preferential survival of CD4+ T cells expressing Thy-1 antigen in Peyer's patches and also in mesenteric lymph nodes, where the relative majority of the surviving CD4-positive T cells displayed CD44hi/CD62Lneg phenotype corresponding to effector memory T-cell features. These CD4-positive T cells also expressed CXCR5 and PD-1 markers characteristic for follicular TH cells (TFH). We also demonstrate that the immediate survival of these cells does not involve proliferation, and simultaneous blockade of IL-7 did not enhance the efficiency of anti-Thy-1 depletion. Induction of germinal center formation in the 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 follicles in the GALT may be favorable for the survival of T-follicular helper cells of memory phenotype, thus allowing their escape during various forms of T-cell depletion.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

Napomena
I.D. je komentor

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