T Cell Interactions in Mycobacterial Granulomas: Non-Specific T Cells Regulate Mycobacteria-Specific T Cells in Granulomatous Lesions
Abstract
:1. Introduction
2. Materials and Methods
2.1. Mice
2.2. Infections
2.3. Testing Transgenic T Cells for Reactivity to PCC-BCG Antigens
2.4. Cell Isolation and Flow Cytometry
2.5. Adoptive Transfer and Immunization
2.6. Immunofluorescence
2.7. Histopathology
2.8. Multiplex Cytokine Assay
3. Results
3.1. D10 T Cells Are Not Activated by PCC-BCG
3.2. Acutely Activated BCG-Non-Specific T Cells Have Access to the Granuloma
3.3. Acute Activation of Local Antigen Non-Specific T Cells Increases the Activation of Granuloma Antigen Specific T Cells
3.4. CA Restimulation of Granuloma-Infiltrating D10 T Cells from CA-Immunized Mice Elicits a Profile of Cytokines That Can Contribute to Protection against Mycobacteria
3.5. PCC-Stimulated Cytokine Secretion by Granuloma Infiltrating Cells Is Upregulated by Recruited Activated BCG-Non-Specific T Cells
3.6. Activation of Non-Specific T Cells Suppresses Cytokine Secretion by BCG-Specific Spleen Cells
3.7. Accumulation of Activated D10 T Cells Results in Increased Granuloma Macrophage Activation
3.8. Effect of Non-Specific T Cells on Granuloma Structure and Function
4. Discussion
4.1. Accumulation of Non-Specific T Cells
4.2. Anergy and Granuloma Function
4.3. Activated D10 T Cells Suppress Systemic PCC-Specific T Cells
5. Summary
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
CA | conalbumin |
PCC | pigeon cytochrome C |
HEL | hen egg lysozyme |
BCG | Mycobacterium bovis strain bacille Calmette-Guérin |
Mtb | M. tuberculosis |
Tg | transgenic |
AFB | acid-fast bacilli |
LCMV | lymphocytic choriomeningitis virus. |
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D10 Transferred, CA Immunized | ||||
---|---|---|---|---|
Spleen | Granuloma | |||
Media | CA | Media | CA | |
Cytokines | ||||
IL-2 | <3.2 | 1894.3 | <3.2 | 520.1 |
IFN-γ | <3.2 | >10,000 | 57 | >10,000 |
TNF | 13.3 | 1323.2 | 145.1 | 488.9 |
IL-17 | <3.2 | 61.1 | 3.9 | 246.9 |
IL-4 | <3.2 | 368 | <3.2 | 118.6 |
IL-5 | <3.2 | 32.6 | 17.7 | 114.7 |
IL-9 | <3.2 | 7.8 | <3.2 | 14.2 |
IL-13 | <3.2 | 414.4 | <3.2 | 86.2 |
IL-1α | <3.2 | 172.8 | 9.3 | 215.7 |
IL-1ß | 12.5 | 211 | 66.9 | 314 |
IL-6 | 83.6 | >18,000 | 4968.2 | 9256.5 |
IL-10 | <3.2 | 231.7 | 81 | 396.2 |
Chemokines | ||||
MIP-1α | 21 | 1401 | 66 | >10,000 |
MCP-1 | 243 | 2101 | 2057 | 1536 |
RANTES | <3.2 | 70 | 84 | 179 |
IP-10 | 237.6 | 400 | 310.6 | 531.5 |
KC | <3.2 | 7 | 333 | 456 |
Macrophage Growth Factors | ||||
GM-CSF | <3.2 | 7439 | 115 | 4908 |
G-CSF | <3.2 | 2034.6 | 858.1 | 1991 |
D10 T cells/106 cells | 8.55 × 104 | 6.7 × 104 |
Spleen | Granuloma | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Nontransfer | D10—No Ag | D10 + CA | Nontransfer | D10—No Ag | D10 + CA | |||||||
Media | PCC | Media | PCC | Media | PCC | Media | PCC | Media | PCC | Media | PCC | |
Cytokines | ||||||||||||
IL-2 | <3.2 | 515.9 | <3.2 | 363.1 | <3.2 | 46.3 | <3.2 | <3.2 | <3.2 | <3.2 | <3.2 | 15.9 |
IFN-γ | <3.2 | >10,000 | <3.2 | >10,000 | <3.2 | 934 | <3.2 | <3.2 | <3.2 | <3.2 | 57 | 377 |
TNF | 6.2 | 455.5 | 7.7 | 494 | 13.3 | 208.9 | 10.7 | 18.6 | 3.9 | 13.5 | 145.1 | 190.5 |
IL-17 | <3.2 | 32 | <3.2 | 6.4 | <3.2 | 9.6 | <3.2 | <3.2 | <3.2 | <3.2 | 3.9 | 72.4 |
IL-4 | <3.2 | 3.7 | <3.2 | 11 | <3.2 | <3.2 | <3.2 | <3.2 | <3.2 | <3.2 | <3.2 | <3.2 |
IL-5 | <3.2 | 12.1 | <3.2 | 10.5 | <3.2 | 3.4 | <3.2 | <3.2 | <3.2 | <3.2 | 17.7 | 45.4 |
IL-9 | <3.2 | <3.2 | 6.5 | 6.5 | <3.2 | <3.2 | 10.1 | <3.2 | <3.2 | <3.2 | <3.2 | <3.2 |
IL-13 | <3.2 | 6.6 | <3.2 | 9.5 | <3.2 | <3.2 | <3.2 | <3.2 | <3.2 | <3.2 | <3.2 | 7.9 |
IL-1α | <3.2 | 114.3 | <3.2 | 105.8 | <3.2 | 9.6 | <3.2 | <3.2 | <3.2 | <3.2 | 9.3 | 27.4 |
IL-1ß | 6.1 | 111.4 | 8.2 | 91.6 | 12.5 | 30.2 | <3.2 | <3.2 | <3.2 | <3.2 | 66.9 | 83.8 |
IL-6 | 15.2 | 7913.2 | 32.8 | 8930.1 | 83.6 | 2486.4 | 489.2 | 633.3 | 45.5 | 66.6 | 4968.2 | 8554.9 |
IL-10 | <3.2 | 91 | 8.3 | 84.1 | <3.2 | 53.4 | <3.2 | 10.5 | <3.2 | <3.2 | 81 | 169.4 |
Chemokines | ||||||||||||
MIP-1α | 22 | 4259 | 34 | 1201 | 21 | 89 | 66 | 126 | 5 | 25 | 66 | 755 |
MCP-1 | 191 | 803 | 338 | 1442 | 243 | 1459 | 465 | 455 | 43 | 55 | 2057 | 2637 |
RANTES | <3.2 | 516 | <3.2 | 379 | <3.2 | 76 | 4 | 11 | <3.2 | 6 | 84 | 184 |
IP-10 | 271.9 | 681.2 | 263.7 | 367.1 | 237.6 | 369.8 | 31.7 | 33.9 | <3.2 | 9.4 | 310.6 | 590 |
KC | <3.2 | 9 | <3.2 | 5 | <3.2 | <3.2 | 75 | 114 | 10 | 14 | 333 | 580 |
Macrophage Growth Factors | ||||||||||||
GM-CSF | <3.2 | 762 | 21 | 1126 | <3.2 | 422 | 15 | 21 | <3.2 | <3.2 | 115 | 354 |
G-CSF | <3.2 | 915.1 | <3.2 | 1254.2 | <3.2 | 408.5 | 51.9 | 73.5 | 9.7 | 16.4 | 858.1 | 2348.3 |
5CC7 T cells/106 cells | 3.9 × 105 | 2.0 × 105 | 1.2 × 105 | 4.0 × 104 | 4.7 × 104 | 1.7 × 104 |
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Co, D.O.; Hogan, L.H.; Karman, J.; Herbath, M.; Fabry, Z.; Sandor, M. T Cell Interactions in Mycobacterial Granulomas: Non-Specific T Cells Regulate Mycobacteria-Specific T Cells in Granulomatous Lesions. Cells 2021, 10, 3285. https://doi.org/10.3390/cells10123285
Co DO, Hogan LH, Karman J, Herbath M, Fabry Z, Sandor M. T Cell Interactions in Mycobacterial Granulomas: Non-Specific T Cells Regulate Mycobacteria-Specific T Cells in Granulomatous Lesions. Cells. 2021; 10(12):3285. https://doi.org/10.3390/cells10123285
Chicago/Turabian StyleCo, Dominic O., Laura H. Hogan, Jozsef Karman, Melinda Herbath, Zsuzsanna Fabry, and Matyas Sandor. 2021. "T Cell Interactions in Mycobacterial Granulomas: Non-Specific T Cells Regulate Mycobacteria-Specific T Cells in Granulomatous Lesions" Cells 10, no. 12: 3285. https://doi.org/10.3390/cells10123285
APA StyleCo, D. O., Hogan, L. H., Karman, J., Herbath, M., Fabry, Z., & Sandor, M. (2021). T Cell Interactions in Mycobacterial Granulomas: Non-Specific T Cells Regulate Mycobacteria-Specific T Cells in Granulomatous Lesions. Cells, 10(12), 3285. https://doi.org/10.3390/cells10123285