Systemic C3 modulates CD8+ T cell contraction after Listeria monocytogenes infection.

Abstract

Ag-specific CD8(+) T cell contraction (contraction), which occurs after the resolution of infection, is critical for homeostasis of the immune system. Although complement components regulate the primary CD8(+) T cell response, there is insufficient evidence supporting their role in regulating contraction and memory. In this study, we show that C3-deficient (C3(-/-)) mice exhibited significantly less CD8(+) T cell contraction than did wild-type mice postinfection with recombinant Listeria monocytogenes expressing OVA. Kinetic analyses also revealed decreased contraction in mice treated with cobra venom factor to deplete C3, which was consistent with the results in C3(-/-) recipient mice transplanted with bone marrow cells from the same donors as wild-type recipient mice. The phenotypes of memory cells generated by C3(-/-) mice were not altered compared with those of wild-type mice. Further, C5aR signaling downstream of C3 was not involved in the regulation of contraction. Moreover, the regulation of contraction by C3 may be independent of the duration of antigenic stimulation or the functional avidity of effector CD8(+) T cells. However, reduced contraction in C3(-/-) mice was accompanied by a decrease in the proportion of KLRG-1(hi) (killer-cell lectin-like receptor G1) CD127(lo) short-lived effector cells at the peak of the response and correlated with a reduction in the levels of inflammatory cytokines, such as IL-12 and IFN-γ, produced early postinfection. These results provide new insights into the role of systemic C3 in regulating contraction following intracellular bacterial infection and may help to develop vaccines that are more effective.

• Authors: Yulong Tan, Yongsheng Li, Xiaolan Fu, Fei Yang, Ping Zheng, Jue Zhang, Bo Guo, Yuzhang Wu
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 193 Issue 7 Pg. 3426-35 (Oct 01 2014) ISSN: 1550-6606 [Electronic] United States
• PMID: 25187659 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 by The American Association of Immunologists, Inc.

Chemical References

• C5ar1 protein, mouse
• Complement C3
• Elapid Venoms
• Immunologic Factors
• Interleukin-7 Receptor alpha Subunit
• Klrg1 protein, mouse
• Lectins, C-Type
• Receptor, Anaphylatoxin C5a
• Receptors, Immunologic
• Interleukin-12
• Interferon-gamma

Topics

• Animals
• CD8-Positive T-Lymphocytes (immunology, pathology)
• Complement C3 (genetics, immunology, pharmacology)
• Elapid Venoms (pharmacology)
• Immunologic Factors (genetics, immunology, pharmacology)
• Immunologic Memory (drug effects, genetics)
• Interferon-gamma (genetics, immunology)
• Interleukin-12 (genetics, immunology)
• Interleukin-7 Receptor alpha Subunit (genetics, immunology)
• Lectins, C-Type
• Listeria monocytogenes (immunology)
• Listeriosis (immunology)
• Mice
• Mice, Inbred BALB C
• Mice, Knockout
• Receptor, Anaphylatoxin C5a (genetics, immunology)
• Receptors, Immunologic (genetics, immunology)
• Signal Transduction (drug effects, genetics, immunology)