CD49d marks Th1 and Tfh-like antigen-specific CD4+ T cells during Plasmodium chabaudi infection

被引:17
作者
Jian, Jiun-Yu [1 ,2 ]
Inoue, Shin-Ichi [1 ,2 ]
Bayarsaikhan, Ganchimeg [1 ]
Miyakoda, Mana [1 ,8 ]
Kimura, Daisuke [1 ,9 ]
Kimura, Kazumi [1 ]
Nozaki, Eriko [3 ]
Sakurai, Takuya [4 ]
Fernandez-Ruiz, Daniel [5 ]
Heath, William R. [5 ]
Yui, Katsuyuki [1 ,2 ,6 ,7 ]
机构
[1] Nagasaki Univ, Grad Sch Biomed Sci, Dept Mol Microbiol & Immunol, Div Immunol, 1-12-4 Sakamoto, Nagasaki 8528523, Japan
[2] Nagasaki Univ, Grad Sch Biomed Sci, Program Nurturing Global Leaders Trop & Emerging, 1-12-4 Sakamoto, Nagasaki 8528523, Japan
[3] Kyorin Univ, Sch Med, Core Lab Prote & Genom, 6-20-2 Shinkawa, Mitaka, Tokyo 1818611, Japan
[4] Kyorin Univ, Sch Med, Dept Mol Predict Med & Sport Sci, 6-20-2 Shinkawa, Tokyo 1818611, Japan
[5] Univ Melbourne, Peter Doherty Inst, Dept Microbiol & Immunol, Melbourne, Vic 3000, Australia
[6] Nagasaki Univ, Sch Trop Med & Global Hlth, 1-12-4 Sakamoto, Nagasaki 8528523, Japan
[7] Nagasaki Univ, Inst Trop Med, 1-12-4 Sakamoto, Nagasaki 8528523, Japan
[8] Nagasaki Univ, Res & Educ Ctr Drug Fostering & Evolut, Sch Pharmaceut Sci, 1-14 Bunkyomachi, Nagasaki 8528521, Japan
[9] Kobe Womens Univ, Fac Hlth & Welf, Dept Hlth Sports & Nutr, Chuo Ku, 4-7-2 Minatojimanakamachi, Kobe, Hyogo 6500046, Japan
基金
日本学术振兴会; 英国医学研究理事会;
关键词
integrin; malaria; BLOOD-STAGE; DENDRITIC CELLS; IFN-GAMMA; MALARIA; HELPER; DIFFERENTIATION; EXPRESSION; RESPONSES; BIOLOGY; BCL6;
D O I
10.1093/intimm/dxab020
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Upon activation, specific CD4(+) T cells up-regulate the expression of CD11a and CD49d, surrogate markers of pathogen-specific CD4(+) T cells. However, using T-cell receptor transgenic mice specific for a Plasmodium antigen, termed PbT-II, we found that activated CD4(+) T cells develop not only to CD11a(hi)CD49d(hi) cells, but also to CD11a(hi)CD49d(lo) cells during acute Plasmodium infection. CD49d(hi) PbT-II cells, localized in the red pulp of spleens, expressed transcription factor T-bet and produced IFN-gamma, indicating that they were type 1 helper T (Th1)-type cells. In contrast, CD49d(lo) PbT-II cells resided in the white pulp/marginal zones and were a heterogeneous population, with approximately half of them expressing CXCR5 and a third expressing Bcl-6, a master regulator of follicular helper T (Tfh) cells. In adoptive transfer experiments, both CD49d(hi) and CD49d(lo) PbT-II cells differentiated into CD49d(hi) Th1-type cells after stimulation with antigen-pulsed dendritic cells, while CD49d(hi) and CD49d(lo) phenotypes were generally maintained in mice infected with Plasmodium chabaudi. These results suggest that CD49d is expressed on Th1-type Plasmodium-specific CD4(+) T cells, which are localized in the red pulp of the spleen, and can be used as a marker of antigen-specific Th1 CD4(+) T cells, rather than that of all pathogen-specific CD4(+) T cells.
引用
收藏
页码:409 / 422
页数:14
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