Altered IFN-gamma and IL-4 pattern lymphokine secretion in mice partially depleted of CD4 T cells by anti-CD4 monoclonal antibody.
Complete elimination of CD4 cells by in vivo treatment with anti-CD4 mAb may result in B cell polyclonal activation. Additionally, mice treated with doses of anti-CD4 that eliminate half the CD4 cells produced higher anti-SRBC antibody responses than controls. This suggests that partial CD4 depletion enhances Th2-like function. To test this hypothesis we examined Th1 and Th2 lymphokine potential in mice partially depleted of CD4 cells. We measured IL-4 and IFN-gamma secretion by stimulated unfractionated spleen cells and analyzed activated, purified CD4 cells by RNA in situ hybridization to determine the percentage of IFN-gamma- or IL-4-producing cells. Unfractionated splenocytes from partially CD4-depleted mice secreted more IL-4 and less IFN-gamma than splenocytes from control mice. In situ hybridization proved that CD4 cells from partially depleted mice contained a higher percentage of IL-4 and a lower percentage of IFN-gamma-producing cells than controls. These results indicate that treatment with a dose of mAb resulting in partial CD4 depletion may permit increased Th2-like lymphokine expression. This study also provides evidence that cells committed to Th2-like function exist in vivo in mice.
Field
E H
EH
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City.
Rouse
T M
TM
Fleming
A L
AL
Jamali
I
I
Cowdery
J S
JS
D000818:Animals; D000911:Antibodies, Monoclonal; D000917:Antibody Formation; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D015870:Gene Expression; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism*; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D008212:Lymphocyte Depletion; D051379:Mice; D008811:Mice, Inbred DBA; D012333:RNA, Messenger / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D000911:Antibodies, Monoclonal; D012333:RNA, Messenger; D015847:Interleukin-4; D007371:Interferon-gamma