CD38+ CD45RB(low) CD4+ T cells: a population of T cells with immune regulatory activities in vitro.
An antibody reactive with CD38 revealed both phenotypic and functional heterogeneity amongst CD45RB(low) cells. Functional analysis of the CD38+ and CD38- fractions showed that the latter contained T cells which responded to recall antigens and produced high levels of cytokine in response to polyclonal stimulation. In contrast, the CD38+ population failed to proliferate or to produce detectable levels of cytokines. Despite appearing unresponsive, the CD38+ population significantly inhibited anti-CD3-induced proliferation and cytokine secretion by the reciprocal CD38- population. Immune suppression required stimulation through the TCR and was dependent on a physical interaction between regulatory and responding CD4+ populations. It did not involve killing of the responding T cells or secretion of IL-10 or TGF-beta. Despite some similarities there is no direct correlation between the in vitro suppression characteristic of the CD38+ CD45RB(low) subset and in vivo suppression which has been shown to be mediated by unseparated CD45RB(low) CD4+ T cells. However, these results demonstrate that two functionally distinct subsets of T cells reside within the antigen-exposed or CD45RB(low) CD4+ T cell population and are thus generated in vivo: (1) conventional memory T cells which proliferate and secrete cytokines in response to activation and (2) a population of regulatory T cells which inhibit T cell activation in vitro. Antibodies reactive with CD38 may provide a useful tool with which to study the role of these T cell subsets in the induction and regulation of the immune response.
Read
S
S
Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, GB.
Mauze
S
S
Asseman
C
C
Bean
A
A
Coffman
R
R
Powrie
F
F
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000032:analysis*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002450:Cell Communication; D016753:Interleukin-10 / Q000378:metabolism; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000032:analysis*; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins; D051379:Mice; D008807:Mice, Inbred BALB C; D009244:NAD+ Nucleosidase / Q000032:analysis*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D011948:Receptors, Antigen, T-Cell; D016753:Interleukin-10; D015847:Interleukin-4; D017493:Leukocyte Common Antigens; D036541:ADP-ribosyl Cyclase; C498155:Cd38 protein, mouse; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1