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T‐Cell development in the absence of a thymus: The number, the phenotype, and the functional capacity of T lymphocytes in nude mice

1984; Wiley; Volume: 170; Issue: 3 Linguagem: Inglês

10.1002/aja.1001700309

1553-0795

Weifeng Chen, Roland Scollay, Ken Shortman, Margot A. Skinner, J. Marbrook,

Monoclonal and Polyclonal Antibodies Research

Abstract A small but definite proportion of T‐lymphocyte‐like cells have been reported in nu/nu (nude) mouse spleen despite the congenital absence of a thymus in these animals. We have determined the number and the characteristics of such cells using flow cytometry. The level of T‐like cells increased with age. In 4‐month‐old nu/nu CBA spleen, 14% of all cells expressed some Thy 1 antigen. However, only 4% expressed mature T‐cell levels, and only the 2% with the highest Thy 1 also showed a normal distribution of Ly 1 and Ly 2 antigens. These T‐like cells were slightly larger than normal nondividing T lymphocytes. We have assessed the total functional capacity of T‐like cells in nu/nu CBA spleen using a high‐cloning‐efficiency limit‐dilution culture system. Almost all precursor cells capable of forming clones when stimulated with concanavalin A in the presence of irradiated spleen cells and growth factors, and almost all precursors of those clones that were cytolytic in a lectin‐mediated tumor‐cell‐lysis assay, were within this 2% subpopulaton of nu/nu spleen cells with mature T‐cell markers. Increased levels of purified interleukin 2 failed to induce further precursor function, indicating that maturation of pre‐T cells was not obtained. However the nu/nu spleen cells bearing mature T‐cell markers displayed only 10‐30% of the cloning efficiency of normal splenic T cells. The majority of nu/nu spleen T‐like cells, even within this phenotypically “normal” subset, appeared to be nonfunctional. We conclude that the absence of a thymus leads to qualitative, as well as quantitative, deficiencies in the T‐cell population, and various interpretations are discussed.