Temporal segregation of 4-1BB versus CD28-mediated costimulation: 4-1BB ligand influences T cell numbers late in the primary response and regulates the size of the T cell memory response following influenza infection.

Abstract

In this report, we demonstrate that CD28(-/-) mice are severely impaired in the initial expansion of D(b)/NP366-374-specific CD8 T cells in response to influenza virus infection, whereas 4-1BB ligand (4-1BBL)(-/-) mice show no defect in primary T cell expansion to influenza virus. In contrast, 4-1BBL(-/-) mice show a decrease in D(b)/NP366-374-specific T cells late in the primary response. Upon secondary challenge with influenza virus, 4-1BBL(-/-) mice show a decrease in the number of D(b)/NP366-374-specific T cells compared to wild-type mice such that the level of the CD8 T cell expansion during the in vivo secondary response is reduced to the level of a primary response, with concomitant reduction of CTL effector function. In contrast, Ab responses, as well as secondary CD4 T cell responses, to influenza are unaffected by 4-1BBL deficiency. Thus, CD28 is critical for initial T cell expansion, whereas 4-1BB/4-1BBL signaling affects T cell numbers much later in the response and is essential for the survival and/or responsiveness of the memory CD8 T cell pool.

• Authors: Edward M Bertram, Peggy Lau, Tania H Watts
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 168 Issue 8 Pg. 3777-85 (Apr 15 2002) ISSN: 0022-1767 [Print] United States
• PMID: 11937529 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 4-1BB Ligand
• Antibodies, Viral
• Antigens, CD
• CD28 Antigens
• Peptide Fragments
• Receptors, Nerve Growth Factor
• Receptors, Tumor Necrosis Factor
• Tnfrsf9 protein, mouse
• Tnfsf9 protein, mouse
• Tumor Necrosis Factor Receptor Superfamily, Member 9
• Tumor Necrosis Factor-alpha
• Viral Core Proteins
• nucleoprotein (366-374), influenza virus

Topics

• 4-1BB Ligand
• Animals
• Antibodies, Viral (biosynthesis)
• Antigens, CD
• CD28 Antigens (physiology)
• CD4-Positive T-Lymphocytes (immunology, pathology)
• CD8-Positive T-Lymphocytes (immunology, pathology)
• Cytotoxicity, Immunologic (genetics)
• Immunization, Secondary
• Immunologic Memory (genetics)
• Influenza A virus (immunology)
• Lymphocyte Activation (genetics)
• Lymphocyte Count
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Orthomyxoviridae Infections (genetics, immunology, virology)
• Peptide Fragments (immunology)
• Receptors, Nerve Growth Factor (deficiency, genetics, metabolism, physiology)
• Receptors, Tumor Necrosis Factor (deficiency, genetics, metabolism, physiology)
• T-Lymphocyte Subsets (immunology, pathology, virology)
• T-Lymphocytes, Cytotoxic (immunology)
• Tumor Necrosis Factor Receptor Superfamily, Member 9
• Tumor Necrosis Factor-alpha (deficiency, genetics, physiology)
• Viral Core Proteins (immunology)