Expression of the costimulatory receptor CD30 is regulated by both CD28 and cytokines.
Costimulation was originally defined and characterized during primary T cell activation. The signaling events that regulate subsequent antigen encounters by T cells are less well defined. In this study we examined the role of CD30 in T cell activation and defined factors that regulate expression of CD30 on T cells. We demonstrate that CD30 expression is restricted to activated T cells and regulated by CD28 signal transduction. In contrast to CD28-expressing TCR Tg cells, CD28-deficient TCR Tg cells did not express CD30 when cultured with peptide and APCs. However, rIL-4 reconstituted CD30 expression on CD28-deficient TCR Tg cells. Blockade of CD28 interactions or depletion of IL-4 inhibited the induction of CD30, suggesting that both CD28 and IL-4 play important roles in the induction of CD30 expression on wild-type cells. However, CD28 signaling did not up-regulate CD30 expression solely through its ability to augment IL-4 production because IL-4-deficient T cells stimulated with anti-CD3 and anti-CD28 expressed CD30. Induction of CD30 in the absence of IL-4 was not due to the IL-4-related cytokine IL-13. CD30, when expressed on an activated T cell, can act as a signal transducing receptor that enhances the proliferation of T cells responding to CD3 crosslinking. Collectively, the data suggest that T cell expression of CD30 is dependent on the presence of CD28 costimulatory signals or exogenous IL-4 during primary T cell activation. Once expressed on the cell surface, CD30 can serve as a positive regulator of mature T cell function.
Gilfillan
M C
MC
Committee on Immunology, Department of Molecular Genetics and Cell Biology, The University of Chicago, IL 60637, USA.
Noel
P J
PJ
Podack
E R
ER
Reiner
S L
SL
Thompson
C B
CB
D000818:Animals; D018106:CD28 Antigens / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D016207:Cytokines / Q000502:physiology*; D007117:Immunization, Secondary; D007166:Immunosuppressive Agents / Q000494:pharmacology; D018793:Interleukin-13 / Q000502:physiology; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D017730:Ki-1 Antigen / Q000096:biosynthesis* / Q000502:physiology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000172:deficiency / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis* / Q000502:physiology; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology
D018106:CD28 Antigens; D016207:Cytokines; D007166:Immunosuppressive Agents; D018793:Interleukin-13; D017730:Ki-1 Antigen; D011948:Receptors, Antigen, T-Cell; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; D015847:Interleukin-4