Chronic parasitic infection maintains high frequencies of short-lived Ly6C+CD4+ effector T cells that are required for protection against re-infection
In contrast to the ability of long-lived CD8(+) memory T cells to mediate protection against systemic viral infections, the relationship between CD4(+) T cell memory and acquired resistance against infectious pathogens remains poorly defined. This is especially true for T helper 1 (Th1) concomitant...
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Published in | PLoS pathogens Vol. 10; no. 12; p. e1004538 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Public Library of Science
01.12.2014
Public Library of Science (PLoS) |
Subjects | |
Online Access | Get full text |
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Summary: | In contrast to the ability of long-lived CD8(+) memory T cells to mediate protection against systemic viral infections, the relationship between CD4(+) T cell memory and acquired resistance against infectious pathogens remains poorly defined. This is especially true for T helper 1 (Th1) concomitant immunity, in which protection against reinfection coincides with a persisting primary infection. In these situations, pre-existing effector CD4 T cells generated by ongoing chronic infection, not memory cells, may be essential for protection against reinfection. We present a systematic study of the tissue homing properties, functionality, and life span of subsets of memory and effector CD4 T cells activated in the setting of chronic Leishmania major infection in resistant C57Bl/6 mice. We found that pre-existing, CD44(+)CD62L(-)T-bet(+)Ly6C+ effector (T(EFF)) cells that are short-lived in the absence of infection and are not derived from memory cells reactivated by secondary challenge, mediate concomitant immunity. Upon adoptive transfer and challenge, non-dividing Ly6C(+) T(EFF) cells preferentially homed to the skin, released IFN-γ, and conferred protection as compared to CD44(+)CD62L(-)Ly6C(-) effector memory or CD44(+)CD62L(+)Ly6C(-) central memory cells. During chronic infection, Ly6C(+) T(EFF) cells were maintained at high frequencies via reactivation of T(CM) and the T(EFF) themselves. The lack of effective vaccines for many chronic diseases may be because protection against infectious challenge requires the maintenance of pre-existing T(EFF) cells, and is therefore not amenable to conventional, memory inducing, vaccination strategies. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Conceived and designed the experiments: NCP DLS. Performed the experiments: NCP PGL EHR LWS AR. Analyzed the data: NCP. Contributed reagents/materials/analysis tools: AJP TWH. Wrote the paper: NCP DLS. Current address: Department of Microbiology Immunology and Infectious Diseases, Cumming School of Medicine, Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta, Canada Current address: Department of Microbiology, University of Washington, Seattle, Washington, United States of America The authors have declared that no competing interests exist. |
ISSN: | 1553-7374 1553-7366 1553-7374 |
DOI: | 10.1371/journal.ppat.1004538 |