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C J Guidos

Publications and source records attributed to C J Guidos.

21 records · Page 2Linked to original sources

Developmental potential of CD4-8- thymocytes. Peripheral progeny include mature CD4-8- T cells bearing alpha beta T cell receptor.

We have used the intra-thymic transfer system to investigate the population dynamics of thymocyte and mature T cell subsets in the absence of continuing precursor input from the bone marrow. We have followed the development and life span of CD4+ and CD8+ thymocyte subsets and mature peripheral T cells from intra-thymically injected adult or fetal CD4-8- thymic precursors. Both precursor types proliferated, differentiated, and exported to peripheral lymphoid tissues alpha beta-TCR+CD4+8- and CD4-8+ progeny which formed a stable, long-lived component of the peripheral T cell pool. The production of phenotypically mature thymocytes and peripheral T cells occurred more rapidly from fetal CD4-8- precursors. CD4+8-:CD4-8+ ratios among peripheral progeny of intra-thymically-injected CD4-8- precursors were initially normal, but they steadily declined among progeny of the fetal precursors. Thus, there appear to be differences in the life span and/or proliferative capacity of mature T cells derived from embryonic vs adult progenitors. In addition to the predominant CD4+8- and CD4-8+ subsets of peripheral T cells, a minor (1 to 20%) population of Thy-1+CD3+4-8- T cells was identified among peripheral progeny of intra-thymically-injected CD4-8- thymocytes, as well as in lymph nodes of unmanipulated animals. A total of 20 to 34% of this subset expressed V beta 8+ TCR and the majority were CD5hi, Pgp-1+, and J11d-. The function and specificity of this newly identified population of thymically derived peripheral T cells remains to be investigated.

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Intrathymic maturation of murine T lymphocytes from CD8+ precursors.

The CD4-8- thymocyte subset contains immature precursors for phenotypically and functionally mature CD4+8- and CD4-8+ thymocytes and peripheral T cells, as well as nonmature CD4+8+ thymocytes, most of which die in situ. The intrathymic death of most thymocytes is probably related to selective influences that ensure that only those precursors bearing self-major histocompatibility complex (MHC)-restricted and self-tolerant T-cell antigen receptors (TCR) survive to complete the maturation process. Interactions between surface molecules on thymocytes (TCR, CD4, and CD8) and thymic stromal cells (MHC proteins) are critical to repertoire selection. To understand this process, the lineage relationships among immature, nonmature, and mature thymocytes must be defined. We have examined directly the precursor-progeny relationships among CD4+8-, CD4-8+, and CD4+8+ murine thymocyte subsets by assessing their short-term (less than 5 days) developmental potentials following intrathymic injection into Thy-1 congenic, unirradiated host mice. Our results identify TCR-/lo CD4-8+ and TCRlo CD4+8+ blast cells as sequential intermediates in the development of mature TCRhi CD4+8- and TCRhi CD4-8+ thymocytes from CD4-8- precursors, thus defining at least one intrathymic maturation pathway for T lymphocytes.

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