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Age-Associated Involution of Cellular Immune Function

I. Accelerated Decline of Mitogen Reactivity of Spleen Cells in Adult Thymectomized Mice¹

From the Department of Pathology, Tumor Biology Unit, University of Florida, ³ Gainesville, Florida 32610

Abstract

Autoimmune-susceptible (A/J and C57BL/6J) and non-autoimmune-susceptible (DBA/1J) strains of mice were adult thymectomized (aTx). Groups of mice, treated by aTx, aTx and 330 rads (R), aTx and 650 R, and 330 R or 650 R only, were compared to normal age-matched control (normal and sham Tx) mice. T cell functions were then followed as measured by in vitro spleen cell responsiveness to the T cell mitogens phytohemagglutinin (PHA) and staphylococcal enterotoxin B (SEB) in a long-term study. A decline in spleen cell responsiveness with natural aging up to 18 months of age was seen to PHA in all three strains and to SEB in A/J and C57BL/6J mice. Adult Tx alone was followed by an accelerated decline in spleen cell responsiveness to PHA and SEB in all three strains of mice. Irradiation combined with aTx-reduced spleen cell responsiveness to SEB in A/J and DBA/1J mice. Irradiation with or without aTx diminished the bone marrow stem cell pool as measured by exogenous colony-forming units, and the hematocrit of all three strains of mice. Thus, the natural decline in cellular immunity with aging was accelerated by aTx in both autoimmune-susceptible and non-autoimmune-susceptible strains of mice. These results emphasize that physiologic thymic function(s) must continue throughout life in order to maintain T cell function.

Footnotes

¹ The research was supported by National Institutes of Health Contract NICHD 72-2760, National Institutes of Health Training Grant AI-00401, and a bequest from the estate of Eli Wilkonson.

² Present address: Department of Veterinary Science, University of Kentucky, Lexington, Kentucky 40506

³ Tumor Biology Unit publication No. 104