Human CD57+ germinal center-T cells are the major helpers for GC-B cells and induce class switch recombination

BMC Immunol. 2005 Feb 4;6:3. doi: 10.1186/1471-2172-6-3.

Abstract

Background: The function of CD57+ CD4+ T cells, constituting a major subset of germinal center T (GC-Th) cells in human lymphoid tissues, has been unclear. There have been contradictory reports regarding the B cell helping function of CD57+ GC-Th cells in production of immunoglobulin (Ig). Furthermore, the cytokine and co-stimulation requirement for their helper activity remains largely unknown. To clarify and gain more insight into their function in helping B cells, we systematically investigated the capacity of human tonsil CD57+ GC-Th cells in inducing B cell Ig synthesis.

Results: We demonstrated that CD57+ GC-Th cells are highly efficient in helping B cell production of all four subsets of Ig (IgM, IgG, IgA and IgE) compared to other T-helper cells located in germinal centers or interfollicular areas. CD57+ GC-Th cells were particularly more efficient than other T cells in helping GC-B cells but not naive B cells. CD57+ GC-Th cells induced the expression of activation-induced cytosine deaminase (AID) and class switch recombination in developing B cells. IgG1-3 and IgA1 were the major Ig isotypes induced by CD57+ GC-Th cells. CD40L, but not IL-4, IL-10 and IFN-gamma, was critical in CD57+ GC-Th cell-driven B cell production of Ig. However, IL-10, when added exogenously, significantly enhanced the helper activity of CD57+ GC-Th cells, while TGF-beta1 completely and IFN-gamma partially suppressed the CD57+ GC-Th cell-driven Ig production.

Conclusions: CD57+CD4+ T cells in the germinal centers of human lymphoid tissues are the major T helper cell subset for GC-B cells in Ig synthesis. Their helper activity is consistent with their capacity to induce AID and class switch recombination, and can be regulated by CD40L, IL-4, IL-10 and TGF-beta.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibody Formation / drug effects
  • Antibody Formation / immunology
  • Antigens, CD / analysis
  • Antigens, Differentiation, T-Lymphocyte / analysis
  • B-Lymphocyte Subsets / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • CD57 Antigens / analysis*
  • Germinal Center / cytology*
  • Germinal Center / immunology
  • Humans
  • Immunoglobulin Class Switching / physiology*
  • Immunoglobulin Isotypes / biosynthesis
  • Interferon-gamma / pharmacology
  • Interleukin-10 / pharmacology
  • Interleukin-4 / pharmacology
  • Lectins, C-Type
  • Lymphocyte Cooperation / drug effects
  • Palatine Tonsil / cytology
  • T-Lymphocyte Subsets / immunology*

Substances

  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD57 Antigens
  • CD69 antigen
  • Immunoglobulin Isotypes
  • Lectins, C-Type
  • Interleukin-10
  • Interleukin-4
  • Interferon-gamma