T cell subsets in the thymus of graft-versus-host immunosuppressed mice. Sensitivity of the L3T4+Lyt-2- subset to cortisone.
We have investigated the effects of graft-versus-host disease on T cell differentiation in the murine thymus. We previously reported that GVH-induced thymic dysplasia results in a T cell immunodeficiency associated with a lack of IL-2 production. This deficiency in IL-2 production may be the result of a reduction in the number of L3T4+Lyt-2- IL-2-producing cells or of a functional defect in this population. To test these two alternatives, flow cytometry analysis of L3T4 and Lyt-2 antigen expression on thymocytes along with immunofluorescence microscopy were employed to assess T cell phenotypes in thymuses of GVH mice. GVH reactions were induced by injecting 40 x 10(6) C57BL/6 (B6) or A strain lymphoid cells into C57BL/6xAF1 (B6AF1) mice. Thymocyte populations were quantitated on different days after GVH induction. In the normal thymus, the ratio of L3T4/Lyt-2 single positive cells was greater than 2:1. In contrast, such a ratio was less than 1:1 in the atrophic GVH thymus, owing to a selective reduction in the number of L3T4+Lyt-2- cells. Following cortisone treatment the ratio of L3T4/Lyt-2 single positive thymocytes in normal F1 mice was approximately 3:1, whereas in GVH animals this ratio was reversed (1:2). This reversal was due to a selective reduction in the absolute numbers of L3T4+Lyt-2- cells. In adrenalectomized GVH animals, thymic cortical atrophy was prevented and normal ratios of L3T4/Lyt-2 single positive cells were observed. However, when these animals were treated with cortisone, the L3+T4/Lyt-2- population was more sensitive than was the L3T4- Lyt2+ population, thereby resulting in a 1:2 L3T4/Lyt-2 ratio. These results demonstrate that single positive L3T4 cells are present in the murine GVH thymus, yet they have not acquired cortisone resistance, a trait normally attributed to this mature thymic subset. It appears that the GVH dysplastic thymus can support the differentiation of L3T4+Lyt-2- cells--however, such a thymus is unable to confer cortisone resistance upon this population. Consequently, these cells appear to be eliminated when exposed to corticosteroids in peripheral lymphoid tissue.
Kornbluth
M
M
Department of Physiology, McGill University, Montreal, Quebec, Canada.
You-Ten
E
E
Desbarats
J
J
Gamache
S
S
Xenocostas
A
A
Lapp
W S
WS
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology; D000315:Adrenalectomy; D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis*; D000950:Antigens, Ly / Q000032:analysis*; D003348:Cortisone / Q000494:pharmacology*; D006086:Graft vs Host Disease / Q000276:immunology; D006087:Graft vs Host Reaction; D007108:Immune Tolerance; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D016176:T-Lymphocyte Subsets / Q000187:drug effects*; D013950:Thymus Gland / Q000276:immunology*
D000945:Antigens, Differentiation, T-Lymphocyte; D000950:Antigens, Ly; D003348:Cortisone