Interferon-gamma preferentially reduces memory/effector CD8 T lymphocytes in healthy subjects.
To evaluate the influence of interferon-gamma (IFN-gamma) on leukocyte dynamics, with a focus on naive and memory T cells, we studied 6 healthy subjects twice in a placebo-controlled trial: once after the administration of recombinant human IFN-gamma (rhIFN-gamma; 100 microg/m2 subcutaneously) and at least 4 weeks later, after the administration of saline solution. Additionally, we studied the expression of adhesion molecules on T lymphocytes after in vitro incubation of whole blood with rhIFN-gamma. IFN-gamma induced a significant depletion in the number of T lymphocytes (P < .05 vs control), which was more severe in the CD8+ cell subset than in the CD4+ T cell subset. The numbers of naive CD4+ T cells and memory CD4+ T cells were equally affected by IFN-gamma, whereas within the CD8+ T cell subset, memory/effector cells disappeared preferentially as compared with naive cells (P < .05 vs control). In addition, IFN-gamma induced a decrease in B cells, NK cells, and monocytes. After an initial increase, granulocyte counts decreased significantly as compared with controls. These effects appeared not to be caused by the minimal rise in plasma cortisol levels (P < .05 vs control). In vitro, IFN-gamma did not up-regulate the expression of CD11a, NKI L16, CD11b, LFA-3, or VLA-4. We conclude that the administration of a single dose of IFN-gamma to healthy subjects profoundly affects the numbers of several leukocyte subsets in the peripheral blood compartment.
de Metz
J
J
Department of Endocrinology and Metabolism, University of Amsterdam, The Netherlands.
Out
T A
TA
Wever
P C
PC
Reijneke
R M
RM
Sprangers
F
F
Sauerwein
H P
HP
Romijn
J A
JA
ten Berge
I J
IJ
D000328:Adult; D018926:Anti-Allergic Agents / Q000032:analysis; D000911:Antibodies, Monoclonal; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000187:drug effects / Q000276:immunology; D018968:CD58 Antigens / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000187:drug effects* / Q000276:immunology*; D005434:Flow Cytometry; D006098:Granulocytes / Q000166:cytology; D006801:Humans; D007156:Immunologic Memory; D039041:Integrin alpha4beta1; D016023:Integrins / Q000032:analysis; D007371:Interferon-gamma / Q000008:administration & dosage* / Q000097:blood / Q000276:immunology*; D007700:Kinetics; D017493:Leukocyte Common Antigens / Q000032:analysis; D007958:Leukocyte Count; D016169:Lymphocyte Function-Associated Antigen-1 / Q000032:analysis; D016177:Macrophage-1 Antigen / Q000032:analysis; D008297:Male; D009000:Monocytes / Q000166:cytology; D016201:Receptors, Lymphocyte Homing / Q000032:analysis
D018926:Anti-Allergic Agents; D000911:Antibodies, Monoclonal; D018968:CD58 Antigens; D039041:Integrin alpha4beta1; D016023:Integrins; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D016201:Receptors, Lymphocyte Homing; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens