In vitro evaluation of γδ T cells regulatory function in Behçet’s disease patients and healthy controls

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• 作者：Antonio Clemente Ximenis^a ; ^b ; ^{ACLEMENTE@clinic.ub.es" class="auth_mail" title="E-mail the corresponding author} ; Catalina Crespí ; Bestard^b ; ^c ; ^{catalina.crespib@ssib.es" class="auth_mail" title="E-mail the corresponding author} ; Ana Cambra Conejero^g ; ^{ainacambra@hotmail.com" class="auth_mail" title="E-mail the corresponding author} ; Lucio Pallaré ; s Ferreres^b ; ^d ; ^{lucio.pallares@ssib.es" class="auth_mail" title="E-mail the corresponding author} ; Antonio Juan Mas^e ; ^{ajuan@hsll.es" class="auth_mail" title="E-mail the corresponding author} ; José ; Luis Olea Vallejo^b ; ^f ; ^{josel.olea@ssib.es" class="auth_mail" title="E-mail the corresponding author} ; Maria Rosa Julià ; Benique^b ; ^g ; ^{rosa.julia@ssib.es" class="auth_mail" title="E-mail the corresponding author}
• 关键词：APC ; antigen presenting cells ; BD ; Behcet&rsquo ; s disease ; CBA ; cytometric bead array ; GD ; γδ T lymphocytes ; GDCD8+ ; CD8-positive γδ T lymphocytes ; GDCD8&minus ; CD8-negative γδ T lymphocytes ; HC ; healthy controls ; LAP ; latency associated peptide ; MFI ; median fluorescence intensity ; nTreg ; naturally occurring T regulatory cells ; Teff ; T effector cells ; Treg ; T regulatory
• 刊名：Human Immunology
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：77
• 期：1
• 页码：20-28
• 全文大小：1586 K

文摘

CD8-positive γδ T lymphocytes (GDCD8⁺) are specifically increased in peripheral blood of Behçet’s disease (BD) patients. GDCD8⁺ have shown a T regulatory (T_reg) function in autoimmune experimental models, human tumor infiltrates and intestinal intraepithelial lymphocytes from celiac patients. The aim of this study was to evaluate the T_reg function of GDCD8⁺ and GDCD8⁻, freshly isolated from peripheral blood, in comparison to CD4⁺CD25^high naturally occurring T_reg cells (nT_reg) in BD and healthy controls (HC).

We tested their suppressive activity on CD4⁺CD25⁻ T effector cells (T_eff) proliferation by a CFSE dilution protocol, after suboptimal activation with anti-CD3, in the absence or presence of IL-2. Furthermore, secreted cytokines and suppressive latency associated peptide (LAP)-TGFβ surface upregulation were determined after GD activation.

We found that Vδ1 chains contribution to GDCD8⁺ was higher in BD than in HC, but neither GDCD8⁺ nor GDCD8⁻; (i) suppressed T_eff proliferation, (ii) expressed LAP-TGFβ (iii) nor secreted IL-10, in either group. Moreover, GD presented a proinflammatory cytokine profile, mainly producing IFNγ and TNFα, in contrast to nT_regs.

In conclusion, peripheral GD could contribute more to the dysregulation of TH1 type of cytokines than to exerting a T_reg function in BD.