CHARACTERIZATION OF 2 DISTINCT PRIMARY T-CELL POPULATIONS THAT SECRETE INTERLEUKIN-2 UPON RECOGNITION OF CLASS-I OR CLASS-II MAJOR HISTOCOMPATIBILITY ANTIGENS

CHARACTERIZATION OF 2 DISTINCT PRIMARY T-CELL POPULATIONS THAT SECRETE INTERLEUKIN-2 UPON RECOGNITION OF CLASS-I OR CLASS-II MAJOR HISTOCOMPATIBILITY ANTIGENS
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DOI:
10.1084/jem.163.3.603
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发表时间:
1986-03-01
影响因子:
15.3
通讯作者:
SINGER, A
SINGER, A
中科院分区:
医学1区
文献类型:
--
作者:
MIZUOCHI, T;ONO, S;SINGER, A

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This study has characterized the primary T cell subpopulations that secrete IL-2 in response to recognition of either class I or class II MHC encoded determinants. The addition to culture of anti-IL-2-R mAb inhibited the consumption of IL-2 by activated lymphocytes during the response period, permitting a much more accurate assessment of the amount of IL-2 produced in the response cultures. Using this response system, we found that primary T cell populations contain two IL-2-secreting T cell subsets that express reciprocal phenotypes and different MHC recognition specificities: an L3T4+,Lyt-2-T cell subset responsive to blood class I and class II MHC alloantigens, and an L3T4-Lyt-2+T cell subset responsive only to class I MHC alloantigens. The L3T4+T cell subset expressed a broad functional response repertoire in that L3T4+T cells were triggered to secrete IL-2 upon recognition of unmodified self-Ia determinants, allogeneic Ia determinants, and class I alloantigens presented by self-Ia determinants. The activation of L3T4+ IL-2-secreting T cells, even those responsive to class I MHC alloantigens, could be blocked completely by anti-Ia mAbs, confirming that the L3T4+T cell subset was in fact class II restricted. In contrast, the Lyt-2+ T cell subset expressed a narrow functional response repertoire in that they were triggered to secrete IL-2 only in response to allogeneic class I MHC determinants, and were not triggered to secrete IL-2 even in response to TNP-modified self-MHC determinants. The specificity of Lyt-2+ IL2-secreting T cells for class I MHC allodeterminants was confirmed by the observations that: (a) their activation could be blocked completely by anti-class I mAbs, (b) they could be triggered by Ia- cell lines which expressed class I MHC alloantigens and possessed accessory function, and (c) they responded to class I MHC alloantigens but failed to respond to class II MHC alloantigens, even in the presence of exogenously added second signals that circumvented the requirement for alloantigen-bearing accessory cells. Finally, the frequency of primary Lyt-2+ T cells that secreted IL-2 in response to class I (Kbml) MHC alloantigens was shown to be only minimally lower than that of L3T4+ T cells that secreted IL-2 in response to class I (I-Abm12) MHC alloantigens. Thus, this study characterizes an Lyt-2+ T cell subset that is present in unprimed T cell populations in unexpectedly high frequency, but functions predominantly, if not exclusively, in immune responses against class I MHC alloantigens.