Blood monocytes, myeloid dendritic cells and the cytokines interleukin (IL)-7 and IL-15 maintain human CD4+ T memory cells with mixed helper/regulatory function.
The number and function of human T cells in the periphery are regulated by homeostatic signals received from antigen-presenting cells (APCs) and the common gamma chain (gammac) cytokines interleukin (IL)-7 and IL-15. We found that, in the absence of introduced antigen, blood monocytes or myeloid dendritic cells (MDCs) in the presence of IL-7 and IL-15 (IL-7/IL-15) can regulate CD4(+) T memory (Tm) cell numbers by polyclonal cell proliferation. The dynamics of CD4(+) Tm cell proliferation, in the presence of IL-7/IL-15, was dependent on contact with MDCs and to a lesser extent on contact with monocytes. IL-7/IL-15 either alone or combined with monocytes or MDCs enhanced the proportion of CD4(+) Tm cells with activated and effector phenotype and diminished the helper function of CD4(+) Tm cells. These CD4(+) Tm cells, preconditioned with IL-7/IL-15 alone or with monocytes or MDCs and IL-7/IL-15, reduced T cell-dependent immunoglobulin M (IgM) and IgG responses. This appeared to be a contact-dependent effect involving a reduction in antibody-producing CD27(+) B memory cells, but contact-independent suppression by soluble factors also contributed to the antibody-producing capacity of CD27(+) B memory cells. These results indicate that blood monocytes, MDCs and the cytokines IL-7/IL-15 contribute to homeostasis of CD4(+) Tm cells by regulating their number, activation state and helper/suppressor (regulatory) function. In healthy individuals, this mode of regulating CD4(+) Tm cell homeostasis may provide a basis for the control of autoimmune responses.
McKinlay
Adam
A
Mater Medical Research Institute, South Brisbane, QLD, Australia.
Radford
Kristen
K
Kato
Masato
M
Field
Ken
K
Gardiner
Damien
D
Khalil
Dalia
D
Burnell
Fiona
F
Hart
Derek
D
Vuckovic
Slavica
S
D017951:Antigen Presentation; D016175:B-Lymphocyte Subsets / Q000276:immunology; D002450:Cell Communication / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology*; D006706:Homeostasis / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D007156:Immunologic Memory; D019409:Interleukin-15 / Q000276:immunology; D015851:Interleukin-7 / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008211:Lymphocyte Cooperation / Q000276:immunology; D009000:Monocytes / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D007074:Immunoglobulin G; D007075:Immunoglobulin M; D019409:Interleukin-15; D015851:Interleukin-7