Immunisation with an allogeneic peptide promotes the induction of antigen-specific MHC II^pos CD4⁺ rat T cells demonstrating immunostimulatory properties

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• 作者：Christoph Otto^a ; ^{Otto_C@chirurgie.uni-wuerzburg.de} ; André ; Heeg^a ; ¹ ; Stefan Kottenmeier^a ; ¹ ; Oliver Kuckein^a ; Bianca Schneiker^b ; ^{Schneiker_B@klinik.uni-wuerzburg.de} ; Sabine Gahn^a ; ^{Gahn_S@chirurgie.uni-wuerzburg.de} ; Christoph Thomas Germer^c ; ^{Germer_C@chirurgie.uni-wuerzburg.de} ; Ulrich Steger^c ; ^{Steger_U@chirurgie.uni-wuerzburg.de}
• 关键词：Allogeneic peptide ; Autostimulation ; T cell-mediated antigen presentation ; MHC class II ; Antigen processing and presentation ; T lymphocytes ; Immunoregulation ; CIITA
• 刊名：Transplant Immunology
• 出版年：2012
• 期刊代码：251_09663274
• 类别：med
• 出版时间：June, 2012
• 卷：26
• 期：4
• 页码：220-229
• 文件大小：764 K

摘要

Background

The phenomenon of T cell stimulation by MHC class II expressing (MHC II^pos) CD4⁺ T cells has been intensively investigated for T cell clones but, so far, not for native T cells. The extensive use of T cell clones may explain the inconsistent outcomes of T cell-mediated antigen-presentation. Therefore, we used freshly isolated primed rat CD4⁺ T cells induced by immunisation with an allogeneic peptide P1, which is involved in allograft rejection.

Methods

MHC II^pos and MHC II^neg CD4⁺ T cells were isolated from popliteal lymph nodes of P1-immunised Lewis rats and were purified by combining depletion and positive selection steps. Purified MHC II^pos CD4⁺ T cells and MHC II^neg CD4⁺ T cells (10⁵ cells per well each) were autostimulated or restimulated with P1-loaded (33 渭g/ml peptide P1) and subsequently irradiated (with 20 Gy) autologous DC.

Results

Seven days after immunisation, a small population of MHC II^pos CD4⁺ T cells was detectable (approximately 8.0%of total lymph node cells), as well as a large population of MHC II^neg CD4⁺ T cells (up to 45%). Antigen-specific proliferation was observed for both T cell populations but only P1-loaded MHC II^pos CD4⁺ T cells presented antigen presenting cell (APC) function for P1-primed T cells. Their inability to activate unprimed T cells may be due to impaired surface expression of costimulatory molecules (CD80 and CD86).

Conclusion

Immunisation with the allogeneic peptide antigen P1 induced antigen-specific MHC II^pos CD4⁺ rat T cells demonstrating perfect APC function for primed T cells in vitro.