Lymphocytes bearing antigen-specific γδ T-cell receptors accumulate in human infectious disease lesions

Abstract

The majority of T cells bear the T-cell receptor (TCR) alpha beta complex which recognizes foreign antigen peptides only in the context of self major histocompatibility complex (MHC) molecules. Such T cells function in a variety of effector roles and secrete cytokines that mediate the activation and differentiation of other cells in the immune system. Recently, a small subpopulation T cells was found to bear a distinct TCR composed of gamma and delta subunits. In man, TCR gamma delta+ cells are distributed as approximately 5 per cent of the CD3+ cells in all organized lymphoid organs as well as in the skin- and gut-associated lymphoid tissues. Although a limited number of germ-line genes encode the TCR gamma and delta subunits, extensive junctional variation particularly in the delta gene, results in unprecedented diversity for this receptor. The nature of the specificity and immunological functions of these T cells remains enigmatic. We report here that in contrast to the normal low frequency of gamma delta-bearing cells in lymphoid tissues, peripheral blood, or normal skin, the frequency is increased five to eightfold in particular granulomatous reactions of leprosy. TCR gamma delta+ lymphocyte lines from these leprosy skin lesions proliferate in vitro specifically to mycobacterial antigens. This reactivity to foreign antigens appears to require presentation in the context of self-molecules. Moreover, culture supernatants from activated gamma delta T lymphocytes induce adhesion and aggregation of bone-marrow monocytes in the presence of granulocyte monocyte-colony stimulating factor (CSF), suggesting that products of gamma delta-bearing T cells may play a role in the immune response, possibly by stimulating granuloma formation.

Gamma/delta T cell clones and natural killer cell clones mediate distinct patterns of non-major histocompatibility complex-restricted cytolysis.

“…The results presented here strongly suggest that human BB3/TiyA + T cells recognize different determinants than non-MHC-restricted NK cells (3,4) or IL-2-activated MHC-restricted a/o T cells (31). The relationship of these target structures to known antigens for y/S T cells remains to be determined (12)(13)(14)32). However, these target structures cannot be related to HLA class I since Daudi cells do not express 02m-associated determinants .…”

“…Indeed, the epitopes on some tumor targets could be related to heat-shock proteins contained in mycobacterial preparations (12-14, 32, 36). It will be interesting to compare the function and specificity of our BB3/TiyA+ clones with BTCSI + clones, other non-MHC-restricted cytolytic y/b T cells (26)(27)(28), and clones derived from different tissues (30,32). Although the physiologic role and function of y/b T cells remains elusive, our data clearly indicate that the recognition of some target cells by our BB3/TiyA+ T cell clones is markedly different from other non-MHC-restricted lymphoid cells.…”

Human γδ-T Lymphocytes Express and Synthesize Connective Tissue Growth Factor: Effect of IL-15 and TGF-β1 and Comparison with αβ-T Lymphocytes

“…They differ from ␣␤-T cells in several parameters, including ontogenic appearance, tissue distribution, and Ag recognition (8). Although increased numbers of ␥␦-T lymphocytes have been observed in a number of infectious diseases (9,10), the physiologic and pathophysisologic roles of the cells in these disorders are not fully understood. There is evidence showing that ␥␦-T cells accumulate during the fibrogenic inflammation underlying wound healing (11) and in human infectious disease lesions (9).…”

“…Although increased numbers of ␥␦-T lymphocytes have been observed in a number of infectious diseases (9,10), the physiologic and pathophysisologic roles of the cells in these disorders are not fully understood. There is evidence showing that ␥␦-T cells accumulate during the fibrogenic inflammation underlying wound healing (11) and in human infectious disease lesions (9). In addition, ␥␦-T cells have been shown to secrete chemotactic factors involved in the recruitment of inflammatory cells (12,13) as well as a number of cytokines (14).…”

Diversity of γδ T-cell antigens

“…[64][65][66]98 However, while many murine cells were found to react with mycobacterial PPD and HSP-65, 66 human mycobacteriareactive cd T cells failed to react with PPD and HSP-65. 99 Searching for alternative Ags, Pfeffer and colleagues 100 found that most human mycobacteria-reactive cd T cells responded to Ags contained in fractions of mycobacterial lysates with a molecular mass of ,3 kDa.…”