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Functional subsets within clonally expanded CD8(+) memory T cells in elderly humans.

W D Chamberlain¹, M T Falta, B L Kotzin

¹Department of Medicine and Department of Immunology, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.

Clinical Immunology (Orlando, Fla.)

|February 29, 2000

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Aging humans show large CD8(+) T cell expansions. Loss of CD28 expression on these cells marks a shift to cytotoxic memory cells, impacting immune function.

Area of Science:

Immunology
Gerontology
Cellular Biology

Background:

Healthy aging is associated with persistent, large clonal expansions of CD8(+) T cells in peripheral blood.
These expanded T cell populations are considered memory cells, but their functional characteristics with age are not fully understood.

Purpose of the Study:

To investigate the functional characteristics of age-associated CD8(+) T cell clones.
To determine the role of CD28 expression in the differentiation and function of these expanded T cell populations.

Main Methods:

Analysis of nine large T cell clones from five elderly individuals.
Flow cytometry to assess CD28 expression on T cells.
In vitro proliferation assays and measurement of perforin expression.

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Main Results:

Expanded CD8(+) T cell clones were predominantly CD28-negative, exhibiting poor proliferation.
CD28-positive fractions within clones showed higher proliferation capacity.
CD28-negative cells displayed increased perforin expression, indicating cytotoxic potential.
CD28 expression loss was observed upon in vitro stimulation.

Conclusions:

Loss of CD28 expression signifies functional differentiation into cytotoxic memory CD8(+) T cells.
This differentiation process is likely a general mechanism within age-associated CD8(+) memory T cell populations.