Established T cell-driven germinal center B cell proliferation is independent of CD28 signaling but is tightly regulated through CTLA-4

J Immunol. 2003 Jan 1;170(1):91-8. doi: 10.4049/jimmunol.170.1.91.

Abstract

CD4 T cell activation is positively (CD28) and negatively (CTLA-4) regulated by the costimulatory ligands CD80 and CD86. A central question is how the balance between these two opposing forces is controlled as T cells differentiate. We have previously shown that CD28 signaling is absolutely required to prime naive CD4 T cells to differentiate into effectors that provide help for germinal centers and class-switched Ab responses. In this study, we show that the requirement for CD28 signaling is transient and effector CD4 T cells do not require CD28 signals to sustain their function. The CD28 independence of effector T cells within germinal centers suggested that a key function for CD80/CD86 under these circumstances might be to provide negative regulatory signals via the CD28 homologue CTLA-4. By examining germinal center responses in mice where the ability to signal through T cell CTLA-4 was compromised, we provide data that supports a critical role for CTLA-4 in down-regulating T cell help for germinal center B cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abatacept
  • Animals
  • Antibodies, Blocking / administration & dosage
  • Antibodies, Monoclonal / administration & dosage
  • Antigens, CD
  • Antigens, Differentiation / genetics
  • Antigens, Differentiation / immunology
  • Antigens, Differentiation / physiology*
  • B-Lymphocyte Subsets / cytology*
  • B-Lymphocyte Subsets / immunology*
  • B-Lymphocyte Subsets / metabolism
  • CD28 Antigens / genetics
  • CD28 Antigens / immunology
  • CD28 Antigens / physiology*
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology*
  • CTLA-4 Antigen
  • Cell Division / genetics
  • Cell Division / immunology
  • Down-Regulation / genetics
  • Down-Regulation / immunology
  • Germinal Center / cytology
  • Germinal Center / immunology
  • Immunoconjugates / genetics
  • Immunoglobulin G / biosynthesis
  • Immunosuppressive Agents / administration & dosage
  • Injections, Intraperitoneal
  • Lymphocyte Cooperation / genetics
  • Lymphocyte Count
  • Mice
  • Mice, Inbred BALB C
  • Mice, Transgenic
  • Signal Transduction / genetics
  • Signal Transduction / immunology*

Substances

  • Antibodies, Blocking
  • Antibodies, Monoclonal
  • Antigens, CD
  • Antigens, Differentiation
  • CD28 Antigens
  • CTLA-4 Antigen
  • Ctla4 protein, mouse
  • Immunoconjugates
  • Immunoglobulin G
  • Immunosuppressive Agents
  • Abatacept