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CD4 cell priming and tolerization are differentially programmed by APCs upon initial engagement.

Amy D Higgins¹, Marianne A Mihalyo, Patrick W McGary

¹Center for Immunotherapy of Cancer and Infectious Diseases, University of Connecticut Health Center, Farmington, CT 06030, USA.

Journal of Immunology (Baltimore, Md. : 1950)

|May 23, 2002

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Immune cells called antigen-presenting cells (APCs) can either tolerate self-antigens or mount an immune response to pathogens. Distinct APCs initiate these distinct CD4+ T cell responses, leading to tolerance or immunity.

Area of Science:

Immunology
Cellular Biology
T cell immunology

Background:

Bone marrow-derived antigen-presenting cells (APCs) play a crucial role in immune responses.
APCs present self-antigens, leading to T cell tolerance, and pathogen-derived antigens, leading to immunity.

Purpose of the Study:

To investigate the distinct parameters that govern tolerogenic versus immunogenic APC function.
To understand the early programming of CD4+ T cell differentiation into tolerogenic or effector cells.

Main Methods:

Utilized a transfer system with naive TCR transgenic hemagglutinin (HA)-specific CD4+ T cells.
Compared T cell responses to constitutively expressed self-HA versus transiently expressed vaccinia-derived HA (viral-HA).
Analyzed phenotypic and functional differences in CD4+ T cells during priming and tolerization.

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Main Results:

Extended viral-HA presentation did not induce tolerization in CD4+ T cells.
Early phenotypic and functional differences were observed in CD4+ T cells during tolerization and priming.
Tolerization to self-HA occurred even when mice were infected with an irrelevant vaccinia virus.

Conclusions:

CD4+ T cell differentiation into tolerogenic or effector lineages is programmed early after APC-T cell interaction.
Pathogen-induced third parties do not explain the differential T cell responses.
Functionally distinct APCs initiate CD4+ T cell tolerance to self-antigens and priming to pathogen-derived antigens.