Development of dermatitis in CD18-deficient PL/J mice is not dependent on bacterial flora, and requires both CD4+ and CD8+ T lymphocytes

CD18-deficient PL/J mice develop dermatitis characterized by hyperkeratosis, and a mixed dermal and epidermal inflammatory infiltrate. The development of this disease requires low-level CD18 expression and at least two PL/J loci. Currently, the mechanisms by which decreased beta(2) integrin expression on leukocytes promotes skin inflammation in PL/J mice are unknown. In these studies, we investigated the role of microbial infection and T lymphocytes in the pathogenesis of this disease. We found that germ-free CD18(-/-) PL/J mice developed dermatitis indistinguishable from that of mice raised in pathogen-free conditions. Adoptive transfer of CD18(-/-) PL/J splenocytes into skin disease-resistant CD18(+/-) PL/J mice failed to induce skin inflammation. However, transfer of CD18(+/-) splenocytes blocked the progression and ultimately led to resolution of skin disease in the majority of CD18(-/-) recipients. Depletion of both CD4(+) and CD8(+) T cells mice prior to onset of the disease significantly delayed the appearance of inflammatory skin disease. In contrast, single depletions of these T cells did not inhibit disease development. These studies show that dermatitis in CD18-deficient PL/J mice is not the consequence of infection, does not require bacterial superantigens, and is mediated by both CD4(+) and CD8(+) T lymphocytes. Furthermore, they suggest that one possible mechanism for skin disease development in these mice may involve the absence or dysfunctional activity of a regulatory T cell population. These mice may therefore be useful in identifying potential mechanisms of pathogenesis and genetic predisposition in human inflammatory skin diseases.     

Human immunedeficiency virus type 1 (HIV-1) disease progression may be due to defects in the expression of the TCR/CD3 complex as well as to a T CD4+ cell deficit

The loss of T CD4+ cells leading to impairment of the immune system is the major cause of disease progression during HIV infection. More recently, the use of highly active anti-retroviral therapy (HAART) has raised important questions regarding the immune system restoration. Idiopathic CD4+ T lymphocytopenia syndrome (ICL) is similar to AIDS, except for the presence of HIV. Despite this similarity, ICL patients have a longer survival time than AIDS cases without HAART. The impairment of TCR/CD3-directed CD4+ T cell immune responses may be responsible for HIV disease progression. We think that the reduction of opportunistic infections which lead to death after HAART, is due to the ability of these memory clones to restore enough clones of the TCR/CD3 complex with fair capacity and diversity to confront frequent pathogens.