Major long-term changes in gamma delta T-cell receptor-positive and CD2+ T-cell subsets after neonatal thymectomy in the pig: a longitudinal study lasting nearly 2 years

Abstract

Blood leucocyte subsets in neonatally (20-day-old) thymectomized (Tx) and sham-thymectomized (STx) pigs were analysed 13 times over nearly 2 years. Tx piglets showed a persistent selective leucopenia, due mainly to a approximately 95% reduction in gamma delta null T cells which fell, with a circulating half-life of approximately 2 weeks, to approximately 0.3 x 10(6)/ml. This residual population was extrathymic in origin since it increased numerically at least approximately eightfold as the Tx pigs grew. Changes in other subsets were complex and affected by antigenic experience associated with weaning and with a change of accommodation at approximately 4 months postoperation (p.o.). Most major populations were increased long-term after thymectomy, especially after 3 months p.o. [i.e. surface (s)IgM+ B cells and CD2+, CD8+, major histocompatibility complex (MHC) class II+, CD4+ and double-positive CD4+ CD8+ T-cell subsets]. However, during the first 3 months, thymectomy caused a significant delay in development of CD8high and CD4+ T cells and, after 4 months p.o., a continuing lack of CD4only (single-positive) T cells. Fortuitous environmental antigenic stimulation caused a major transient lymphocytosis, with counts increasing 1.2-fold in STx and 3.5-fold in Tx pigs. This was largely due to an increase in CD2+ CD8+ MHC class II+ T cells, particularly in Tx pigs. The small residual thymus-independent gamma delta null subset also increased, while gamma delta T cells in STx pigs actually decreased. Evolving changes in expression of CD45, CD45R, CD44, CD18 and very late antigen type-4 (VLA-4) also occurred following thymectomy. Thus, the most persistent long-term effect of thymectomy, other than the lack of gamma delta null T cells, was the markedly increased numbers of double-positive (CD4+ CD8low) T cells, most of which expressed MHC class II and higher levels of adhesion molecules.