Rapid establishment of a stable IL-4/IFN-gamma production profile in the antigen-specific CD4+ T cell response to protein immunization.
Development of the antigen-specific murine T cell response to immunization with keyhole limpet hemocyanin (KLH) in adjuvant has been monitored with direct limiting dilution analysis of CD4+ cells in draining lymph nodes (LN) and measurement of the cytokines produced by their clonal progeny. In vivo, the response to immunization suggested a major role for IL-4 and a minor role for IFN-gamma since IL-4 mRNA levels increased and IFN-gamma mRNA levels declined in LN over the first 3 days, and KLH-specific serum antibodies were mainly of IgG1 class with lower levels of IgE and IgG2a. Antigen-specific clonogenic cells were first detected in LN at day 4, at which time they comprised approximately 8% of the total CD4+ LN cell pool, declining to 1-2% from day 7 until at least 6 weeks after immunization. These clonogenic cells expressed high levels of surface CD44 (Pgp-1) both early and late in the in vivo response. Over the whole of the time span from day 4 to 6 weeks after immunization, most antigen-specific cells gave rise to clones that secreted IL-4 and a smaller proportion gave rise to IFN-gamma-secreting clones. By contrast, polyclonally activated CD4+ cells from untreated mice preferentially gave rise to clones with the converse cytokine profile. We conclude that a stable ratio of antigen-specific CD4+ cells committed to IL-4 or IFN-gamma synthesis is established within the first 4 days after KLH immunization and, contrary to prediction, does not evolve towards a more restricted cytokine profile during the primary response.
Kelso
A
A
Walter and Eliza Hall Institute of Medical Research, PO Royal Melbourne Hospital, Victoria, Australia.
Groves
P
P
Troutt
A B
AB
Pech
M H
MH
D000818:Animals; D000941:Antigens / Q000276:immunology*; D001886:Bordetella pertussis / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002352:Carrier Proteins / Q000032:analysis; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006433:Hemocyanins / Q000276:immunology; D018960:Hyaluronan Receptors; D007136:Immunoglobulins / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000096:biosynthesis*; D008198:Lymph Nodes / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface / Q000032:analysis; D016201:Receptors, Lymphocyte Homing / Q000032:analysis
D000941:Antigens; D002352:Carrier Proteins; D018960:Hyaluronan Receptors; D007136:Immunoglobulins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D016201:Receptors, Lymphocyte Homing; D015847:Interleukin-4; D007371:Interferon-gamma; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin