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National Institute for Medical Research, London, United Kingdom
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
(p5676, or p186205 or p177199), were uniformly Th1 type,
releasing only IFN-
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 ß-chains in their recognition of p186205, released
either (IFN-
and IL-5) or (IFN-
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 p120139 secreted either (IFN-
only) or (IFN-
and IL-5) or (IFN-
and IL-2
and IL-5) on activation. Despite such phenotypic
diversity within the individuals repertoire, all clones had been
maintained under identical in vitro culture conditions. Moreover,
sequence analyses of TCR ß gene usage indicated that in most
instances clones from the same donor expressed identical
(VDJ)ß rearrangements, indicative of a common progenitor cell.
FACS analysis of cytoplasmic cytokine production confirmed that for the
novel phenotype (IFN-
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.
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