Two sequential activation modules control the differentiation of protective T helper-1 (Th1) cells
| Autor: | Ryan A. Langlois, Michael F. Goldberg, Kevin C. Osum, Marc K. Jenkins, Peter D. Krueger, Dmitri I. Kotov, Thamotharampillai Dileepan, Sung-Wook Hong |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
CD4-Positive T-Lymphocytes Male Cellular differentiation Immunology Cell Biology Lymphocyte Activation Cell Line 03 medical and health sciences Interferon-gamma 0302 clinical medicine Interferon medicine Immunology and Allergy Animals Cytotoxicity Pathogen Phagosome Cell Differentiation T-Lymphocytes Helper-Inducer Th1 Cells Interleukin-12 Cell biology Mice Inbred C57BL 030104 developmental biology Infectious Diseases medicine.anatomical_structure Cell culture 030220 oncology & carcinogenesis Interleukin 12 Drosophila Female medicine.drug |
| Zdroj: | Immunity. 54(4) |
| ISSN: | 1097-4180 |
| Popis: | Summary Interferon-γ (IFN-γ)-producing CD4+ T helper-1 (Th1) cells are critical for protection from microbes that infect the phagosomes of myeloid cells. Current understanding of Th1 cell differentiation is based largely on reductionist cell culture experiments. We assessed Th1 cell generation in vivo by studying antigen-specific CD4+ T cells during infection with the phagosomal pathogen Salmonella enterica (Se), or influenza A virus (IAV), for which CD4+ T cells are less important. Both microbes induced T follicular helper (Tfh) and interleukin-12 (IL-12)-independent Th1 cells. During Se infection, however, the Th1 cells subsequently outgrew the Tfh cells via an IL-12-dependent process and formed subsets with increased IFN-γ production, ZEB2-transcription factor-dependent cytotoxicity, and capacity to control Se infection. Our results indicate that many infections induce a module that generates Tfh and poorly differentiated Th1 cells, which is followed in phagosomal infections by an IL-12-dependent Th1 cell amplification module that is critical for pathogen control. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|