B7+ T cells in myeloma: an acquired marker of prior chronic antigen presentation.
Murine T cells do not endogenously upregulate CD80 expression but rather acquire CD80 from antigen presenting cells (APC) during CD28 ligation. Murine CD80+ memory T cells undergo apoptosis in the presence of high levels of antigen while naive CD80+ T cells are capable of acting as APC and T cell:T cell ligation induces anergy and unresponsiveness to antigen rechallenge. Reversing T cell unresponsiveness may be a key factor in the development of immunotherapy strategies for patients with myeloma. We have determined that B7+ T cells (CD80+ or CD86+) are common in patients with myeloma (n = 45), can be either CD4 or CD8, tend to be associated with stable disease and are polyclonal memory T cells (CD45RO). CD80 mRNA expression was present in CD80+ monocytes but not in CD3+ cells with a similar level of CD80 antigen expression. CD80 and CD86 antigen expression was upregulated on B cells but not T cells during incubation with trimeric human CD40 ligand (huCD40LT) + IL-2. Although there was a gradual loss of expression during in vitro culture, CD80+ T cells could be purified for further study. We conclude that B7 expression is common on T cells of patients with myeloma but that this is acquired rather than endogenously produced. B7+ CD45RO+ T cells constitute a population of memory T cells chronically exposed to antigen and warrant further study.
Brown
Ross
R
Institute of Haematology, Royal Prince Alfred Hospital, Sydney, NSW Australia. rbrown@haem.rpa.cs.nsw.gov.au
Murray
Allan
A
Pope
Belinda
B
Sze
Daniel
D
Gibson
John
J
Ho
P Joy
PJ
Joshua
Doug
D
D000818:Animals; D017951:Antigen Presentation; D015703:Antigens, CD / Q000096:biosynthesis; D000943:Antigens, Differentiation / Q000096:biosynthesis; D017209:Apoptosis; D018122:B7-1 Antigen / Q000096:biosynthesis*; D051940:B7-2 Antigen; D018106:CD28 Antigens / Q000096:biosynthesis; D017252:CD3 Complex / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D060908:CTLA-4 Antigen; D002469:Cell Separation; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007156:Immunologic Memory; D007167:Immunotherapy / Q000379:methods; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D009101:Multiple Myeloma / Q000097:blood*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000378:metabolism*; D015854:Up-Regulation
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; D017252:CD3 Complex; C497964:CD86 protein, human; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C497965:Cd86 protein, mouse; C556707:Ctla4 protein, mouse; D018076:DNA, Complementary; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; D017493:Leukocyte Common Antigens