Distinct CD4⁺ helper T cells involved in primary and secondary responses to infection

Helper T cells are critical for protective immunity, CD8 ⁺ T-cell memory, and CD4 ⁺ recall responses, but whether the same or distinct CD4 ⁺ T cells are involved in these responses has not been established. Here we describe two CD4 ⁺ T cells, LLO118 and LLO56, specific for an immunodominant Listeria...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2012-06, Vol.109 (24), p.9511-9516
Main Authors: Weber, K. Scott, Li, Qi-Jing, Persaud, Stephen P, Campbell, Jeff D, Davis, Mark M, Allen, Paul M
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Antigens
Bacterial infections
Biological Sciences
CD4-positive T-lymphocytes
CD4-Positive T-Lymphocytes - cytology
CD4-Positive T-Lymphocytes - immunology
CD4-Positive T-Lymphocytes - microbiology
CD8-Positive T-Lymphocytes - immunology
Cell Proliferation
Cellular biology
Coinfection
Cytometry
Down regulation
epitopes
Epitopes - chemistry
Epitopes - immunology
Immunity
Immunity (Disease)
Infections
Listeria
Listeria monocytogenes
Listeria monocytogenes - immunology
Memory
Mice
Mice, Transgenic
Molecular Sequence Data
secondary infection
Sequence Homology, Amino Acid
T cell antigen receptors
T cell receptors
T lymphocytes
Transgenic animals
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Summary:Helper T cells are critical for protective immunity, CD8 ⁺ T-cell memory, and CD4 ⁺ recall responses, but whether the same or distinct CD4 ⁺ T cells are involved in these responses has not been established. Here we describe two CD4 ⁺ T cells, LLO118 and LLO56, specific for an immunodominant Listeria monocytogenes epitope, with dramatically different responses to primary and secondary infection. Comparing in vivo responses, LLO118 T cells proliferate more strongly to primary infection, whereas surprisingly, LLO56 has a superior CD4 ⁺ recall response to secondary infection. LLO118 T cells provide more robust help for CD8 ⁺ T-cell responses to secondary infection than LLO56. We found no detectable differences in antigen sensitivity, but naive LLO118 T cells have much lower levels of CD5 and their T-cell receptor levels are dramatically down-regulated after their strong primary response. Thus, distinct CD4 ⁺ helper T cells are specialized to help either in primary or secondary responses to infection.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1202408109