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Aging and Decreased Cutaneous Immunity: Lack of TNF- May Be the Answer

Insufficient tumor necrosis factor affected the ability of T lymphocytes to migrate to the skin.

Our ability to mount immune responses in the skin declines with age, which is thought to be the major reason that older individuals are more susceptible to cutaneous infections and skin cancer. The basis for this decline is unclear. Now, researchers have examined the movement of regulatory and memory T cells during delayed hypersensitivity reaction in elders.

They found significantly lower cutaneous recall responses to intradermal bacterial and viral antigens in older (70) than in younger (40) subjects (P<0.0001). In vitro, surprisingly, the peripheral blood mononuclear cells of many of the older individuals responded normally to the same recall antigens, indicating that the loss of immunity was localized to the skin while systemic immunity to these antigens in blood was unchanged. Although the loss of cutaneous immunity was associated with a lower-than-normal number of CD4⁺ T cells in the dermal infiltrate, their ability to migrate into the skin was unaffected. Rather, the ability of the dermal macrophages to produce TNF- was markedly reduced in the older individuals compared with the younger group. Macrophage production is known to increase expression of adhesion molecules on dermal microvascular endothelial cells, which are required for movement of T cells into sites of cutaneous antigen exposure. The inability of macrophages to produce TNF- may explain the deficient cutaneous immune responses to the skin-test antigens.

Comment: This careful analysis identified one possible mechanism by which cutaneous immunity diminishes with age. This information provides a basis for the development of targeted therapies that could reverse the immunological deficit. Correcting the age-related defect in cutaneous immunity with agents that augment the migration of T lymphocytes from the blood to the skin may reduce the relatively high incidence of cutaneous infections and skin cancer in the older population.

— Craig A. Elmets, MD

Published in Journal Watch Dermatology October 9, 2009

Citation(s):

Agius E et al. Decreased TNF- synthesis by macrophages restricts cutaneous immunosurveillance by memory CD4⁺ T cells during aging. J Exp Med 2009 Aug 31; 206:1929.

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• TNF and Aging
  saka venkata satya prasad, 12 Oct 2009 3:07 AM EST
  The article is an eye opener for the role of TNF in the skin. Immunology has played a vital role... [more]
• Aging and Decreased Cutaneous Immunity: Lack of TNF- May Be the Answer
  Lucy D. McNamara, R.Ph., Massachusetts General Hospital, 26 Oct 2009 2:40 PM EST
  Correlating these results with serum vitamin D lelvels and serum cathelicidin levels would be very interesting.