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Original Article

Ruben Dyall^a and Janko Nikoli-ugi^a,b

^a Laboratory of T Cell Development, Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021
^b Weill Graduate School of Medical Sciences of the Cornell University, New York, New York 10021
Box 98, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10021.212-794-4019212-639-2387

nikolicj{at}mskcc.org

The majority (70%) of postselection CD4⁺ single-positive (SP) thymocytes are CD8^loCD4^hi. These cells express very low levels of CD8, undetectable by flow cytofluorimetric (FCM) analysis, but sufficiently high to allow purification by panning. Unlike the fully mature CD8^–CD4^hi thymocytes, which account for the remaining 30% of the SP CD4⁺ thymocytes, CD8^loCD4^hi cells are functionally immature and short-lived unless they receive an unidentified maturation signal from the thymus. In this study, we tested the hypothesis that this signal is provided by a T cell receptor (TCR)–major histocompatibility complex (MHC) class II interaction. Using intrathymic transfer, we show that the immature CD8^loCD4^hi cells could complete their intrathymic maturation and populate the peripheral lymphoid organs in the absence of MHC class II (and class I) molecules. Furthermore, in mice devoid of class II (and class I) molecules, the progeny of CD8^loCD4^hi cells was long-lived and functionally reactive to allogeneic class II molecules, although their numbers in the spleen and the mesenteric lymph node were 40–50% lower than those in class II⁺ mice 5 mo after transfer. Control experiments demonstrated that the surviving cells did not originate from the contaminating mature thymocytes. These results demonstrate that the final maturation, proliferation, and peripheral survival (up to 5 mo) of at least some postselection CD4⁺ SP cells do not require the TCR–MHC class II interaction. They also indicate that the TCR–MHC class II interaction(s) required for the intrathymic development of long-lived CD4⁺ SP cells occurs before the CD4^hi SP stage of development.

Key Words: CD4 thymocytes • T cell receptor • T cell development • major histocompatibility complex class II

1used in this paper: B6, C57BL/6; CII–, MHC class II–deficient by gene targeting disruption; CI/II–, deficient for both MHC class I and class II molecules; DC, dendritic cell; DP, CD8+CD4+ double-positive; FCM, flow cytofluorometry; M, macrophage(s); MFI, mean fluorescence intensity; mLN, mesenteric LN; SP, single-positive

© 1999 The Rockefeller University Press

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