Selective migration of the human helper‐inducer memory T cell subset: confirmation by in vivo cellular kinetic studies

Abstract

The vast majority of T cells present in chronic inflammatory lesions are of the helper-inducer/memory (CD45RO+CD29+) phenotype; suppressor-inducer/naive cells (CD45RA+) are virtually absent. Furthermore, CD4+ T cells are found more frequently than CD8+ cells. Previous in vitro studies have suggested that this may be, in part, due to the increased capacity of CD45RO+CD29+ T cells to bind to endothelium and, thus, enter inflammatory foci but no in vivo evidence for preferential migration exists. To investigate this, suction blisters were generated over a purified protein derivative of tuberculin-induced delayed-type hypersensitivity lesions in humans and the phenotype of the blister cells was studied. At all time points, a preponderance of CD45RO+CD29+ cells over CD45RA+ cells and of CD4 over CD8 cells was demonstrated. Because of the rapid kinetics, this appears to represent preferential migration of these cell types rather than in situ proliferation or phenotype conversion. In addition the expression of the CD45RO but not the CD45RA antigen was up-regulated on blister T cells compared to blood T cells. Analysis of blister fluid showed high concentrations of interleukin 6 but not tumor necrosis factor-alpha or lymphotoxin. This study shows for the first time directly in vivo that CD45RO+ T cells migrate preferentially into inflammatory lesions. Furthermore, it illustrates the potential usefulness of this system in the analysis of the early phases of the immune inflammatory response.

The Cutaneous Response in Humans toTreponema pallidumLipoprotein Analogues Involves Cellular Elements of Both Innate and Adaptive Immunity

“…In this model (29), mild suction is used to elicit blister formation at the dermo-epidermal junction following intradermal injection with treponemal lipopeptides. In contrast with the paucity of cells in fluid from blisters raised over salineinjected skin or unmanipulated normal skin, fluid within blisters elicited over sites of inflammation contains numerous extravasated immune cells that can be analyzed by flow cytometry (30 -33); comparison with peripheral blood (PB) enables one to identify selectively recruited leukocyte subsets and to assess the influence of the inflammatory microenvironment on their state of activation/ differentiation (31)(32)(33). There is now extensive evidence that the composition of cells in blister fluid accurately reflects the cellular infiltrates within the underlying dermis (30 -33).…”

Subpopulations of primed t helper cells in rheumatoid arthritis

“…Almost all synovial T cells are primed, expressing high levels of an isoform of the leukocyte common antigen termed CD45RO (5,6). Primed and activated T cells appear to enter the joint in a nonspecific manner because of their high level of expression of adhesion molecules (7). The strongly biased population that results is very likely to have a different pattern of activity compared with unselected peripheral blood cells (2).…”

Imbalance of CD4+ lymphocyte subsets in patients with mixed connective tissue disease

“…Others have observed later expression of the memory cell phenotype by the vast majority of PHA-stimulated T cells from healthy individuals [11,13,14], Changes were not due to increased cell proliferation, and consistent with this, conversion into the memory cell phenotype has not been found to be necessarily correlated with proliferation [31], Increased expression of adhesion molecules might lead to facilitated localization of memory T cells to the inflamed tissue [32], In this regard, Pitzalis et al [33] have demonstrated the preponderance of CD4+CD29+UCHL1 + cells in the rheumatic joint, and in other inflammatory lesions [34], In addition, CD29+ memory T cells have been shown to have a greater ability to adhere to vascular endothelium than their CD29c ounterpart [35], Therefore, enhanced expression of CD29 and other adhesion molecules might lead to accumulation of CD4+ memory cells at tissue sites, and could result in depletion ofthis cell subset in the peripheral blood of patients with MCTD, Interestingly, activated T cells and a high proportion of CD4+ cells have been detected in the infiltrated skin of PSS patients with recent onset of disease [36], It remains to be clarified whether the imbalance of CD4+ cell subsets might lead to reduced suppressor T cell function in patients with MCTD, Similar to Melendro et al [7], we observed diminished numbers of CD8+ cells in MCTD, Data obtained earlier by Alarcjon-Segovia & Ruiz-Arguelles [6] suggest that anti-RNP antibodies might cause deletion of suppressor T cells. It might be considered that altered responsiveness and lymphokine secretion of CD4+ cell subsets exert indirect effects on CDS"*" cells by enhancing B cell activity.…”