Functional Heterogeneity in CD4(+) T Cell Responses Against a Bacterial Pathogen

Area of Science:

• Immunology
• Microbial Pathogenesis
• T cell Biology

Background:

• CD4(+) T cells are crucial for adaptive immunity against bacterial infections.
• T cell receptor (TCR) affinity is a key factor in T cell activation and function.
• Distinct T cell responses are observed even when T cells recognize the same antigen.

Purpose of the Study:

• To investigate how CD4(+) T cells with identical in vitro responses exhibit different in vivo functions.
• To determine the role of self-pMHC signaling strength in dictating peripheral T cell responses.
• To explore the contribution of CD5 and self-interaction in T cell maintenance and function.

Main Methods:

• Generation of two transgenic mouse lines (LLO56 and LLO118) recognizing the same Listeria monocytogenes epitope.
• In vitro and in vivo assessment of T cell responses during primary and secondary infections.
• Analysis of T cell responses to both TCR-mediated and non-specific stimuli.

Main Results:

• LLO56 and LLO118 T cells showed identical in vitro responses but vastly different in vivo functions.
• LLO118 dominated primary responses and CD8 T cell help, while LLO56 predominated in secondary responses.
• Distinct T cell responses were elicited by specific and non-specific stimuli, linked to self-pMHC signaling strength during development.

Conclusions:

• The strength of self-pMHC signaling during T cell development critically shapes peripheral immune responses.
• TCR affinity to foreign and self-pMHC molecules influences the outcome of immune responses.
• A spectrum of T cell responses exists, contributing to immune system diversity in combating pathogens.