The CD27- subset of peripheral blood memory CD4+ lymphocytes contains functionally differentiated T lymphocytes that develop by persistent antigenic stimulation in vivo.
On the basis of expression of the T cell differentiation antigen CD27, human peripheral blood CD4+ memory cells can be divided into two subsets, a large CD45RA-CD27+ (82%) and a small CD45RA-CD27- (18%) population. Analysis of the functional properties of these memory T cell subsets showed that proliferative responses to the recall antigen tetanus toxoid (TT), shortly after booster immunization, were mainly confined to the CD27- population. Also, in atopic individuals, proliferative responses to allergens for which these individuals are sensitized, were limited to the CD45RA-CD27- population. After stimulation with CD3 monoclonal antibody and phorbol ester, CD27+ cells produced vast amounts of interleukin (IL)-2 but minimal amounts of IL-4, whereas in marked contrast, CD27- T cells secreted low levels of IL-2 and high levels of IL-4. The capacity of the vast majority of these latter cells to produce IL-4 was found to be a stable feature since high IL-4 secreting T cell clones were generated from the CD27- subset. These findings suggest that upon renewed as well as chronic antigenic stimulation in vivo, memory T cells acquire the CD45RA-CD27- phenotype and that, as a consequence, in this subset functionally differentiated CD4+ T cells are compartmentalized. Our results predict that analysis of the small CD27- subset of memory cells, that makes up approximately 10% of the peripheral blood T cell population, will provide information on the specificity and function of responding CD4+ T cells at a given point in time in healthy and diseased individuals.
Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam.
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R
De Jong
M
M
Brouwer
B
B
Hooibrink
T
T
Van der Pouw-Kraan
F
F
Miedema
R A
RA
Van Lier
D000941:Antigens / Q000008:administration & dosage; D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D002999:Clone Cells; D015870:Gene Expression; D006649:Histocompatibility Antigens / Q000032:analysis; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics; D017493:Leukocyte Common Antigens; D008213:Lymphocyte Activation; D012333:RNA, Messenger / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7
D000941:Antigens; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D006649:Histocompatibility Antigens; D007376:Interleukin-2; D012333:RNA, Messenger; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D015847:Interleukin-4; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens