Single-cytokine-producing CD4 memory cells predominate in type 1 and type 2 immunity.
The patterns of Ag-induced cytokine coexpression in normal, in vivo-primed CD4 memory T cells has remained controversial because the low frequency at which these cells occur has effectively prevented direct ex vivo measurements. We have overcome this limitation by using two-color cytokine enzyme-linked immunospot assays and computer-assisted image analysis. We found CD4 memory cells that simultaneously expressed IL-2, IL-3, IL-4, IL-5, and IFN-gamma to be rare (0-10%). This cytokine segregation was seen in adjuvant-induced type 1, type 2, and mixed immunity to OVA, in Leishmania infection regardless of the Ag dose used or how long after immunization the assay was performed. The data suggest that type 1 and type 2 immunity in vivo is not mediated by classic Th1 or Th2 cells but by single-cytokine-producing memory cells.
Karulin
A Y
AY
Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.
Hesse
M D
MD
Tary-Lehmann
M
M
Lehmann
P V
PV
D000818:Animals; D000953:Antigens, Protozoan / Q000008:administration & dosage; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005620:Freund's Adjuvant / Q000008:administration & dosage / Q000276:immunology; D007089:Image Enhancement; D007156:Immunologic Memory; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D007377:Interleukin-3 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D016773:Leishmaniasis, Cutaneous / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
D000953:Antigens, Protozoan; D016207:Cytokines; D007376:Interleukin-2; D007377:Interleukin-3; D015848:Interleukin-5; C111390:OVA 323-339; D010446:Peptide Fragments; D015847:Interleukin-4; D007371:Interferon-gamma; D010047:Ovalbumin; D005620:Freund's Adjuvant