Human CD57+ germinal center-T cells are the major helpers for GC-B cells and induce class switch recombination.
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.
Kim
Jong R
JR
Laboratory of Immunology and Hematopoiesis, Department of Pathobiology, Bioscience Center, VPTH Room 126, 725 Harrison St, Purdue University, West Lafayette, IN 47907, USA. kim41@purdue.edu
Lim
Hyung W
HW
Kang
Seung G
SG
Hillsamer
Peter
P
Kim
Chang H
CH
D000917:Antibody Formation / Q000187:drug effects / Q000276:immunology; D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018959:CD57 Antigens / Q000032:analysis*; D018858:Germinal Center / Q000166:cytology* / Q000276:immunology; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000502:physiology*; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis; D007371:Interferon-gamma / Q000494:pharmacology; D016753:Interleukin-10 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D037181:Lectins, C-Type; D008211:Lymphocyte Cooperation / Q000187:drug effects; D014066:Palatine Tonsil / Q000166:cytology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018959:CD57 Antigens; D007132:Immunoglobulin Isotypes; D007371:Interferon-gamma; D016753:Interleukin-10; D015847:Interleukin-4; D037181:Lectins, C-Type; D000099192:CD69 Antigens