Novel diversity in Th1, Th2 type differentiation of hemagglutinin-specific T cell clones elicited by natural influenza virus infection in three major haplotypes (H-2b,d,k).
We report novel diversity in the lymphokine (LK) secretion profile of hemagglutinin-specific, CD4+ T cell clones elicited by influenza virus infection in three major haplotypes: I-Ad- or I-Ed-restricted T cell clones obtained from individual BALB/c donors, and specific for three distinct antigenic peptides (p56-76, or p186-205 or p177-199), were uniformly Th1 type, releasing only IFN-gamma on activation. In contrast, extensive diversity was evident for the C57BL/10 or CBA/Ca repertoire. Sibling T cell clones, established from the same C57BL/10 donor and expressing identical TCR beta-chains in their recognition of p186-205, released either (IFN-gamma and IL-5) or (IFN-gamma and IL-4 and IL-5) or (IL-4 and IL-5 and IL-10) following Ag-specific or nonspecific stimulation. Similarly, I-Ak-restricted T cell clones, specific for p120-139 secreted either (IFN-gamma only) or (IFN-gamma and IL-5) or (IFN-gamma and IL-2 and IL-5) on activation. Despite such phenotypic diversity within the individual's repertoire, all clones had been maintained under identical in vitro culture conditions. Moreover, sequence analyses of TCR beta gene usage indicated that in most instances clones from the same donor expressed identical (VDJ)beta rearrangements, indicative of a common progenitor cell. FACS analysis of cytoplasmic cytokine production confirmed that for the novel phenotype (IFN-gamma and IL-5), both LKs were synthesized at the single cell level. Sibling families of T cell clones, established from a common donor following viral infection but differing in LK secretion, may offer a suitable model system for further studies of signal transduction mechanisms that discriminate between Th1- and Th2-specific responses to a well defined protective Ag.
Graham
C M
CM
National Institute for Medical Research, Mill Hill, London, United Kingdom.
Smith
C A
CA
Thomas
D B
DB
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D002999:Clone Cells / Q000166:cytology / Q000276:immunology / Q000821:virology; D005260:Female; D006183:H-2 Antigens / Q000235:genetics*; D006239:Haplotypes; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D016130:Immunophenotyping; D009980:Influenza A virus / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D008222:Lymphokines / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D006183:H-2 Antigens; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D000949:Histocompatibility Antigens Class II; D015848:Interleukin-5; D008222:Lymphokines; D016693:Receptors, Antigen, T-Cell, alpha-beta; D007371:Interferon-gamma