IL-2 producing memory CD4+ T lymphocytes are closely associated with the generation of IgG-secreting plasma cells.
The role of specific CD4(+) T cell subsets in the induction of humoral immune responses in humans is largely unknown. In this study, the generation of hepatitis B surface Ag-specific CD4(+) T lymphocytes following vaccination was closely monitored and characterized at the single-cell level. The appearance and absolute numbers of hepatitis B surface Ag-specific IL-2 producing effector memory CD4(+) T lymphocytes was solely and tightly related to Ab titers reached. This relation remained present many years after vaccination. Subsequently, a relation was found between Ab titers and number of IL-2 producing memory CD4(+) T lymphocytes for various other Ags. These observations matched the findings of an in vitro assay, using different T cell subsets to induce B cell differentiation into IgG-producing plasma cells. By depleting for IL-2 producing memory T cells, we demonstrated that these cells are important for B cell differentiation into IgG-producing plasma cells. Finally, blocking the action of IL-2 with an IL-2R-alpha Ab inhibited the differentiation of B lymphocytes into IgG-producing plasma cells. Based on these findings, we conclude that the development of Ag-specific IL-2-producing memory T cells appears to be essential for the development of IgG-secreting plasma cells in humans.
Litjens
Nicolle H R
NH
Department of Internal Medicine, Division of Nephrology, Erasmus Medical Center, Rotterdam, The Netherlands. n.litjens@erasmusmc.nl
Huisman
Martin
M
Hijdra
Daniëlle
D
Lambrecht
Bart M N
BM
Stittelaar
Koert J
KJ
Betjes
Michiel G H
MG
D000328:Adult; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000166:cytology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G; D007156:Immunologic Memory; D007376:Interleukin-2 / Q000096:biosynthesis / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D010950:Plasma Cells / Q000166:cytology* / Q000378:metabolism; D016176:T-Lymphocyte Subsets
D006514:Hepatitis B Surface Antigens; D007074:Immunoglobulin G; D007376:Interleukin-2