| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Shortman, Ken Kato, Yu Zotos, Dimitra Tarlinton, David M. Zaid, Ali Davey, Gayle M. Lahoud, Mireille H. Nutt, Stephen L. Mueller, Scott N. Heath, William R. Caminschi, Irina |
| Description |
Author Affiliation: Kato Y ( Department of Microbiology and Immunology, The Peter Doherty Institute, The University of Melbourne, Parkville, Victoria 3010, Australia); Zaid A ( Department of Microbiology and Immunology, The Peter Doherty Institute, The University of Melbourne, Parkville, Victoria 3010, Australia); Davey GM ( Department of Microbiology and Immunology, The Peter Doherty Institute, The University of Melbourne, Parkville, Victoria 3010, Australia); Mueller SN ( Department of Microbiology and Immunology, The Peter Doherty Institute, The University of Melbourne, Parkville, Victoria 3010, Australia); Nutt SL ( Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia); Zotos D ( Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia); Tarlinton DM ( Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia); Shortman K ( Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia); Lahoud MH ( Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Victoria 3004, Australia); Heath WR ( Department of Microbiology and Immunology, The Peter Doherty Institute, The University of Melbourne, Parkville, Victoria 3010, Australia); Caminschi I ( Department of Microbiology and Immunology, The Peter Doherty Institute, The University of Melbourne, Parkville, Victoria 3010, Australia) |
| Abstract |
Targeting Ags to dendritic cell (DC) surface receptors can induce a variety of responses depending on the DC type targeted, the receptor targeted, and the adjuvant used. Clec9A (DNGR-1), which is expressed by CD8(+) DCs, has been shown to bind F-actin exposed on damaged cells. Targeting Ag to this receptor in mice and nonhuman primates induces strong humoral immunity even in the absence of adjuvant, a process seen for a few select DC receptors. In contrast with other receptors, however, targeting Clec9A induces long-lived, affinity-matured Ab responses that are associated with efficient CD4(+) T cell responses shown to possess properties of follicular Th cells (TFH). In this article, we provide definitive evidence that Clec9A targeting promotes the development of TFH by showing that responding CD4 T cells express CXCR5, PD1, the TFH transcription factor Bcl6, and the cytokine IL-21, and that these cells localize to germinal centers. Furthermore, we extend studies from the model Ag OVA to the viral Ag glycoprotein D of HSV-1 and examine the capacity of primed TFH to form functional memory. We show that targeting glycoprotein D to Clec9A even in the absence of adjuvant induced long-lived memory CXCR5(+) PD1(hi) CD4(+) T cells that proliferated extensively upon secondary challenge and rapidly developed into effector TFH. This was associated with enhanced germinal center B cell responses and accelerated Ab production. Our study indicates that targeting Ags to Clec9A in the absence of adjuvant routinely generates TFH responses that form long-lived memory capable of robust secondary TFH responses. |
| ISSN |
00221767 |
| e-ISSN |
15506606 |
| Journal |
The Journal of Immunology |
| Issue Number |
3 |
| Volume Number |
195 |
| Language |
English |
| Publisher |
The American Association of Immunologists |
| Publisher Date |
2015-08-01 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Dendritic Cells Immunology Immunologic Memory Lectins, C-type Lymphocyte Activation Receptors, Immunologic T-lymphocytes, Helper-inducer Adoptive Transfer Animals Antigens B-lymphocytes Cell Differentiation Dna-binding Proteins Biosynthesis Germinal Center Cytology Interleukin-21 Receptor Alpha Subunit Genetics Interleukins Mice Mice, Inbred C57bl Mice, Knockout Ovalbumin Programmed Cell Death 1 Receptor Proto-oncogene Proteins C-bcl-6 Receptors, Cxcr5 Transplantation Viral Envelope Proteins Research Support, Non-u.s. Gov't Discipline Immunology |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Immunology and Allergy Immunology |
