Impairment of rat thymocyte differentiation and functions by neonatal capsaicin treatment is associated with induction of apoptosis

The direct and indirect interaction between the nervous system and its tran smitters with the immune system was evaluated in the rat by using the neuro toxin capsaicin (Caps). In the present study we investigated the effect of Caps administration to neonatal rats on thymocyte subpopulation distributio n and functions at different times after treatment. Caps, treatment results in a marked reduction of thymus weight and cellularity. As shown by immuno fluorescence and FACS analysis, profound depletion of double negative (DN), double positive (DP), and single positive (SP) CD4(+) cells was already ev ident at day 7 after treatment and persisted until day 28. Reduced numbers of SP CD8(+) cells were observed only at later time points. Analysis of TCR phenotype indicates that CD5(+) TCR gamma/delta(+) are particularly sensit ive to neonatal Caps treatment. Caps-induced thymocyte depletion was associ ated with reduced proliferation in response to T cell mitogens. Moreover, i n situ TUNEL reaction and agarose gel electrophoresis indicate that neonata l Caps treatment induces apoptosis of thymus cells. Morphological analysis reveals the presence of apoptotic cells in the subcapsular thymus cortical region. Overall our results suggest that Caps when administered at birth, p rofoundly affects T cell differentiation, likely through its ability to act ivate apoptotic cell death program. (C) 2000 Elsevier Science B.V. All righ ts reserved.